Next Article in Journal
Effects of Sorafenib and Quercetin Alone or in Combination in Treating Hepatocellular Carcinoma: In Vitro and In Vivo Approaches
Next Article in Special Issue
Impact of N-Linked Glycosylation on Therapeutic Proteins
Previous Article in Journal
Curcuma longa L. Rhizome Extract as a Poly(vinyl chloride)/Graphene Nanocomposite Green Modifier
Previous Article in Special Issue
Stereoselective Synthesis of 2-Deoxythiosugars from Glycals
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 27
Issue 22
10.3390/molecules27228083
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

An Overview of Antitumour Activity of Polysaccharides

by
Hongzhen **
1,
Maohua Li
1,
Feng Tian
1,
Fan Yu
2,* and
Wei Zhao
1,3,*
1
College of Pharmacy, Nankai University, 38 Tongyan Road, **nan District, Tian** 300350, China
2
College of Life Sciences, Nankai University, Wei** Road, Nankai District, Tian** 300350, China
3
State Key Laboratory of Medicinal Chemical Biology, Nankai University, 38 Tongyan Road, **nan District, Tian** 300350, China
*
Authors to whom correspondence should be addressed.
Molecules 2022, 27(22), 8083; https://doi.org/10.3390/molecules27228083
Submission received: 28 October 2022 / Revised: 14 November 2022 / Accepted: 17 November 2022 / Published: 21 November 2022
(This article belongs to the Special Issue Carbohydrate-Based Drugs Discovery)
Browse Figures
Versions Notes

Abstract

:
Cancer incidence and mortality are rapidly increasing worldwide; therefore, effective therapies are required in the current scenario of increasing cancer cases. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, and they have become the focus of current antitumour drug research owing to their significant antitumour effects. In addition to the direct antitumour activity of some natural polysaccharides, their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in natural polysaccharides and polysaccharide-based nanomedicines for cancer therapy.

1. Introduction

In the coming years, cancer is expected to become the main cause of death and the most important obstacle to extending life expectancy in the world. Lung cancer is the most common cancer and the leading cause of cancer death (18.4% of total cancer deaths), closely followed by colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) [1]. There are three common cancer therapeutics, including surgery, radiation therapy, and chemotherapy, as well as other emerging therapies, such as molecular targeted therapy. However, the serious side effects and drug resistance of chemotherapy and other treatments are becoming major obstacles in current cancer research. Hence, it is very important to develop a new type of anticancer agent with ideal antitumour activity and extremely low toxicity.
Polysaccharides are carbohydrates that participate in almost all aspects of organisms and play various important biological functions [2]. Polysaccharides consist of 10 or more monosaccharides linked together by glycosidic bonds, which can be linear or contain branched chains. Importantly, monosaccharide composition, molecular weight (MW), and polysaccharide attachment affect its structure, and its structure further affects its properties and functional mechanisms [3]. According to their source, polysaccharides can be classified into natural polysaccharides and semisynthetic polysaccharides. Natural polysaccharides are distributed in many organisms. Then, the natural polysaccharide is further chemically or enzymatically modified to obtain semisynthetic polysaccharides. So far, researchers have found that polysaccharides have a wide range of biological effects, including anticancer, antibiotic, antioxidant, anticoagulant, and immuno-stimulation activities.
The antitumor effect of polysaccharides was first discovered by Nauts et al. in 1946, which can effectively relieve the symptoms of cancer patients [4]. Ample evidence indicated that polysaccharides can inhibit tumors through direct anticancer activity, such as inducing apoptosis of tumor cells and inhibiting migration (Table 1). In addition, the structure of polysaccharides provides versatility for the synthesis of multi-functional nanocomposites, which can achieve high stability and bioavailability through chemical modification, thus delivering therapeutic drugs to tumor tissues [5]. This review used keywords (anticancer/polysaccharides/drug delivery systems/nanomedicines) to search in PubMed and Web of Science databases, and selected qualified high-level papers for systematic sorting and summary. In this paper, we aim to systematically summarize the research findings in the past decade, and the different structures of anticancer polysaccharides from different sources and polysaccharide-based nanomedicines for cancer treatment are reviewed, which provides theoretical support for the design and development of polysaccharide preparations.

2. Polysaccharides from Plants

2.1. Panax ginseng C. A. Meyer Polysaccharides

Panax ginseng C. A. Meyer (P. ginseng) is a precious medicine that has been used for thousands of years, also known as ginseng [6]. Ginseng is composed of multiple active components, including ginsenosides and polysaccharides. Studies have proven that polysaccharides are one of the most important components in P. ginseng and participate in immunomodulation, antitumour, and antidiabetic activities [7].
P. ginseng polysaccharide contains starch-like glucans and pectin [8]. Pectin is a plant-derived neutral polysaccharide with abundant resources for its amounts and categories. Many types of pectin polysaccharides are associated with anticancer activity. Pectin, with Panax ginseng C. A. Meyer Polysaccharidesvery complex structure, typically contains galacturonic acid (GalA), galactose (Gal), arabinose (Ara), and rhamnose (Rha) residues [9]. Pectin could be divided into five types: homogalacturonan (HG), type I rhamnogalacturonans (RG-I), type II rhamnogalacturonans (RG-II), xylagalgalacturonan (XGA), and Apio galgalacturonan (AGA), based on the different structural characteristics [10]. HG is characterized by α-(1→4)-D-GalA repeat units as the backbone [11], whereas RG-I is composed of Ara, galactans, and L-fucose (L-fuc) in the sidechains [12]. RG-II and XGA are both derivatives of HG [10]. The components of P. ginseng pectin include HG and RG-I, as well as GalA, Gal, Ara, and Rha [13].
To date, many kinds of pectin have been isolated and identified from ginseng, and some of them have been identified as having antitumour activity, as described in Table 2.
Ginseng polysaccharide could also significantly inhibit the growth of Lewis lung carcinoma tumor [19]. In addition, one selenium-modified polysaccharide, sGP, has been reported. The experimental results indicate that sGP enhances apoptosis in HL-60 cells, demonstrating that chemical modification methods to obtain high contents of selenium polysaccharides could be developed as a novel antitumour therapy [20].

2.2. Angelica Sinensis (Oliv.) Diels Polysaccharides

The root of A. sinensis, known as Danggui, is a celebrated Chinese medicinal herb [21]. A. sinensis possesses a wide range of pharmacological activities, including hematopoiesis, immunomodulation, antioxidant, and anticancer activities [22,23,24,25]. Polysaccharides are the most important active constituents in Danggui, and numerous A. sinensis polysaccharides (ASPs) have been identified. The majority of ASPs contain GalA, Gal, Ara, Rha, mannose (Man), and glucose (Glc) with various molar ratios. Wei et al. also proved that APSs could induce apoptosis in cancer cells via regulation of the JAK/STAT of the transcription pathway [26]. Key kinases in the JAK/STAT and PI3K/AKT pathways were also downregulated by ASPs’ stimulation in another study [27]. ASPs have also been utilized in drug delivery systems. Wang et al. prepared doxorubicin (DOX)-loaded nanoparticles and proved that it can inhibit the growth of HepG2 multicellular spheres [28].

2.3. Portulaca oleracea L. Polysaccharides

P. oleracea L., a traditional Chinese herbal medicine, is known as MaChi** various nanocarriers. Drug delivery methods based on polysaccharides nanomaterials help to achieve targeted delivery of immunotherapeutic agents to immune cell subtypes and effectively improve the therapeutic effect of drug carriers. In addition, the degradation products of polysaccharides are normal monosaccharides in vivo and can be recycled by cells without accumulation in the tissue.
In a word, this article reviews the latest progress of polysaccharides and polysaccharide-based nanomaterials and their applications in cancer immunotherapy. The anticancer properties of polysaccharides are mainly mediated through two ways: (I) direct cytotoxicity and (II) as a targeted nano carrier platform, which carries traditional anticancer drugs. Although there are still many unsolved problems in this field, the clinical value and broad application prospects of anticancer polysaccharides make them an important direction of new drug development.

Author Contributions

Writing original draft preparation, H.J.; writing review and editing, H.J., M.L. and F.T.; visualization and supervision, W.Z. and F.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the National Key R&D Program of China (2018YFA0507204) and the National Natural Science Foundation of China (22077068) and the Fundamental Research Funds for the Central Universities.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [Green Version]
  2. Schjoldager, K.T.; Narimatsu, Y.; Joshi, H.J.; Clausen, H. Global view of human protein glycosylation pathways and functions. Nat. Rev. Mol. Cell Biol. 2020, 21, 729–749. [Google Scholar] [CrossRef]
  3. Li, N.; Wang, C.; Georgiev, M.I.; Bajpai, V.K.; Tundis, R.; Gandara, J.S.; Lu, X.; **ao, J.; Tang, X.; Qiao, T. Advances in dietary polysaccharides as anticancer agents: Structure-activity relationship. Trends Food Sci. Technol. 2021, 111, 360–377. [Google Scholar] [CrossRef]
  4. Zong, A.; Cao, H.; Wang, F. Anticancer polysaccharides from natural resources: A review of recent research. Carbohydr. Polym. 2012, 90, 1395–1410. [Google Scholar] [CrossRef]
  5. Zeng, Y.; **ang, Y.; Sheng, R.; Tomás, H.; Rodrigues, J.; Gu, Z.; Zhang, H.; Gong, Q.; Luo, K. Polysaccharide-based nanomedicines for cancer immunotherapy: A review. Bioact. Mater. 2021, 6, 3358–3382. [Google Scholar] [CrossRef] [PubMed]
  6. Liu, L.; Xu, F.-R.; Wang, Y.Z. Traditional uses, chemical diversity and biological activities of Panax, L. (Araliaceae): A review. J. Ethnopharmacol. 2020, 263, 112792. [Google Scholar] [CrossRef] [PubMed]
  7. Zhao, B.; Lv, C.; Lu, J. Natural occurring polysaccharides from Panax ginseng C. A. Meyer: A review of isolation, structures, and bioactivities. Int. J. Biol. Macromol. 2019, 133, 324–336. [Google Scholar] [CrossRef]
  8. Sun, L.; Wu, D.; Ning, X.; Yang, G.; Lin, Z.; Tian, M.; Zhou, Y. α-Amylase-assisted extraction of polysaccharides from Panax ginseng. Int. J. Biol. Macromol. 2015, 75, 152–157. [Google Scholar] [CrossRef]
  9. Sun, L.; Ropartz, D.; Cui, L.; Shi, H.; Ralet, M.C.; Zhou, Y. Structural characterization of rhamnogalacturonan domains from Panax ginseng C. A. Meyer. Carbohydr Polym. 2019, 203, 119–127. [Google Scholar] [CrossRef]
  10. Yue, F.; Xu, J.; Zhang, S.; Hu, X.; Wang, X.; Lü, X. Structural features and anticancer mechanisms of pectic polysaccharides: A review. Int. J. Biol. Macromol. 2022, 209, 825–839. [Google Scholar] [CrossRef]
  11. Maxwell, E.G.; Belshaw, N.J.; Waldron, K.W.; Morris, V.J. Pectinan emerging newbioactive food polysaccharide. Trends Food Sci. Technol. 2012, 24, 64–73. [Google Scholar] [CrossRef]
  12. Shakhmatov, E.G.; Makarova, E.N.; Belyy, V.A. Structural studies of biologically active pectin-containing polysaccharides of pomegranate Punica granatum. Int. J. Biol. Macromol. 2019, 122, 29–36. [Google Scholar] [CrossRef] [PubMed]
  13. Zhang, X.; Yu, L.; Bi, H.; Li, X.; Ni, W.; Han, H.; Li, N.; Wang, B.; Zhou, Y.; Tai, G. Total fractionation and characterization of the water-soluble polysaccharides isolated from Panax ginseng C.A. Meyer. Carbohydr. Polym. 2009, 77, 544–552. [Google Scholar] [CrossRef]
  14. Li, C.; Cai, J.; Geng, J.; Li, Y.; Wang, Z.; Li, R. Purification, characterization and an-ticancer activity of a polysaccharide from Panax ginseng. Int. J. Biol. Macromol. 2012, 51, 968–973. [Google Scholar] [CrossRef]
  15. Cai, J.-P.; Wu, Y.-J.; Li, C.; Feng, M.Y.; Shi, Q.T.; Li, R.; Wang, Z.Y.; Geng, J.S. Panax ginseng polysaccharide suppresses metastasis by modulating Twist expression in gastric cancer. Int. J. Biol. Macromol. 2013, 57, 22–25. [Google Scholar] [CrossRef]
  16. Li, C.; Tian, Z.-N.; Cai, J.P.; Chen, K.X.; Zhang, B.; Feng, M.Y.; Shi, Q.T.; Li, R.; Qin, Y.; Geng, J.S. Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer. Carbohydr. Polym. 2014, 102, 103–109. [Google Scholar] [CrossRef]
  17. Gao, X.; Zhi, Y.; Sun, L.; Peng, X.; Zhang, T.; Xue, H.; Tai, G.; Zhou, Y. The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng pectin on galectin-3 and its structure-activity relationship. J. Biol. Chem. 2013, 288, 33953–33965. [Google Scholar] [CrossRef] [Green Version]
  18. Jia, H.; Zhao, B.; Zhang, F.; Santhanam, R.K.; Wang, X.; Lu, J. Extraction, structural characterization, and anti-hepatocellular carcinoma activity of polysaccharides from Panax ginseng meyer. Front. Oncol. 2021, 11, 4905. [Google Scholar] [CrossRef]
  19. Zhou, X.; Shi, H.; Jiang, G.; Zhou, Y.; Xu, J. Antitumour activities of ginseng polysaccharide in C57BL/6 mice with Lewis lung carcinoma. Tumor Biol. 2014, 35, 12561–12566. [Google Scholar] [CrossRef]
  20. Liao, K.; Bian, Z.; **e, D.; Peng, Q. A selenium-modified ginseng polysaccharide promotes the apoptosis in human promyelocytic leukemia (HL-60) cells via a mitochondrial-mediated pathway. Biol. Trace Elem. Res. 2017, 177, 64–71. [Google Scholar] [CrossRef]
  21. Chen, X.-P.; Li, W.; **ao, X.F.; Zhang, L.L.; Liu, C.X. Phytochemical and pharmacological studies on Radix Angelica sinensis. Chin. J. Nat. Med. 2013, 11, 577–587. [Google Scholar] [CrossRef] [PubMed]
  22. Younas, F.; Aslam, B.; Muhammad, F.; Mohsin, M.; Raza, A.; Faisal, M.N.; Hassan, S.; Majeed, W. Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats. Pharm. Biol. 2017, 55, 108–113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Pan, S.; Jiang, L.; Wu, S. Stimulating effects of polysaccharide from Angelica sinensis on the nonspecific immunity of white shrimps (Litopenaeus vannamei). Fish Shellfish Immun. 2018, 74, 170–174. [Google Scholar] [CrossRef]
  24. Wang, Y.; Li, X.; Chen, X.; Zhao, P.; Qu, Z.; Ma, D.; Zhao, C.; Gao, W. Effect of stir-frying time during Angelica Sinensis Radix processing with wine on physicochemical, structure properties and bioactivities of polysaccharides. Process Biochem. 2019, 81, 188–196. [Google Scholar] [CrossRef]
  25. Zhou, W.-J.; Wang, S.; Hu, Z.; Zhou, Z.Y.; Song, C.J. Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation. Biochem. Biophys. Res. Commun. 2015, 467, 562–569. [Google Scholar] [CrossRef]
  26. Fu, Z.; Li, Y.; Yang, S.; Ma, C.; Zhao, R.; Guo, H.; Wei, H. Angelica sinensis polysaccharide promotes apoptosis by inhibiting JAK/STAT pathway in breast cancer cells. Trop. J. Pharm. Res. 2019, 18, 2247–2253. [Google Scholar]
  27. Yang, J.; Shao, X.; Jiang, J.; Sun, Y.; Wang, L.; Sun, L. Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y. Cell Biol. Int. 2018, 42, 867–876. [Google Scholar] [CrossRef]
  28. Zhang, Y.; Cui, Z.; Mei, H.; Xu, J.; Zhou, T.; Cheng, F.; Wang, K. Angelica sinensis polysaccharide nanoparticles as a targeted drug delivery system for enhanced therapy of liver cancer. Carbohydr. Polym. 2019, 219, 143–154. [Google Scholar] [CrossRef]
  29. Tleubayeva, M.I.; Datkhayev, U.M.; Alimzhanova, M.; Ishmuratova, M.Y.; Korotetskaya, N.V.; Abdullabekova, R.M.; Flisyuk, E.V.; Gemejiyeva, N.G. Component composition and antimicrobial activity of CO2 extract of portulaca oleracea, growing in the territory of kazakhstan. Sci. World J. 2021, 2021, 1–10. [Google Scholar] [CrossRef]
  30. Kim, K.-H.; Park, E.-J.; Jang, H.J.; Lee, S.J.; Park, C.S.; Yun, B.S.; Lee, S.W.; Rho, M.C. 1-Carbomethoxy-β-Carboline, derived from portulaca oleracea L., ameliorates LPS-mediated inflammatory response associated with MAPK signaling and nuclear translocation of NF-κB. Molecules 2019, 24, 4042. [Google Scholar] [CrossRef] [Green Version]
  31. Tian, X.; Ding, Y.; Kong, Y.; Wang, G.; Wang, S.; Cheng, D. Purslane (Portulacae oleracea L.) attenuates cadmium-induced hepatorenal and colonic damage in mice: Role of chelation, antioxidant and intestinal microecological regulation. Phytomedicine 2021, 92, 153716. [Google Scholar] [CrossRef]
  32. Zhang, W.; Zheng, B.; Deng, N.; Wang, H.; Li, T.; Liu, R.H. Effects of ethyl acetate fractional extract from Portulaca oleracea L. (PO-EA) on lifespan and healthspan in Caenorhabditis elegans. J. Food Sci. 2020, 85, 4367–4376. [Google Scholar] [CrossRef]
  33. Shena, H.; Tang, G.; Zeng, G.; Yang, Y.; Cai, X.; Li, D.; Liu, H.; Zhou, N. Purification and characterization of an antitumour polysaccharide from Portulaca oleracea L. Carbohydr. Polym. 2013, 93, 395–400. [Google Scholar] [CrossRef] [PubMed]
  34. Zhao, R.; Gao, X.; Cai, Y.; Shao, X.; Jia, G.; Huang, Y.; Qin, X.; Wang, J.; Zheng, X. Antitumour activity of Portulaca oleracea L. polysaccharides against cervical carcinoma in vitro and in vivo. Carbohydr. Polym. 2013, 96, 376–383. [Google Scholar] [CrossRef] [PubMed]
  35. Zhao, R.; Zhang, T.; Ma, B.; Li, X. Antitumour activity of portulaca oleracea L. polysaccharide on heLa cells through inducing TLR4/NF-kB signaling. Nutr. Cancer 2017, 69, 131–139. [Google Scholar] [CrossRef] [PubMed]
  36. Zhao, R.; Shao, X.; Jia, G.; Huang, Y.; Liu, Z.; Song, B.; Hou, J. Anti-cervical carcinoma effect of Portulaca oleracea L. polysaccharides by oral administration on intestinal dendritic cells. BMC Complement. Altern. Med. 2019, 19, 1–10. [Google Scholar] [CrossRef]
  37. Park, Y.M.; Lee, H.Y.; Kang, Y.G.; Park, S.H.; Lee, B.G.; Park, Y.J.; Oh, H.G.; Moon, D.I.; Kim, Y.P.; Park, D.S.; et al. Immune-enhancing effects of Portulaca oleracea L.-based complex extract in cyclophosphamide-induced splenocytes and immunosuppressed rats. Food Agric. Immunol. 2018, 30, 13–24. [Google Scholar] [CrossRef] [Green Version]
  38. Jia, G.; Shao, X.; Zhao, R.; Zhang, T.; Zhou, X.; Yang, Y.; Li, T.; Chen, Z.; Liu, Y. Portulaca oleracea L. polysaccharides enhance the immune efficacy of dendritic cell vaccine for breast cancer. Food Function 2021, 12, 4046–4059. [Google Scholar] [CrossRef]
  39. Zhuang, S.; Ming, K.; Ma, N.; Sun, J.; Wang, D.; Ding, M.; Ding, Y. Portulaca oleracea L. polysaccharide ameliorates lipopolysaccharide-induced inflammatory responses and barrier dysfunction in porcine intestinal epithelial monolayers. J. Funct. Foods 2022, 91, 104997. [Google Scholar] [CrossRef]
  40. Masci, A.; Carradori, S.; Casadei, M.A.; Paolicelli, P.; Petralito, S.; Ragno, R.; Cesa, S. Lycium barbarum polysaccharides: Extraction, purification, structura characterization and evidence about hypoglycaemic and hypolipidaemic effects. A review. Food Chem. 2018, 254, 377–389. [Google Scholar] [CrossRef]
  41. Amagase, H.; Farnsworth, N.R. A review of botanical characteristics, phytochemistry, clinical relevance in efficacy and safety of Lycium barbarum fruit (GOJI). Food Res. Int. 2011, 44, 1702–1717. [Google Scholar] [CrossRef]
  42. Chen, F.; Ran, L.; Mi, J.; Yan, Y.; Lu, L.; **, B.; Li, X.; Cao, Y. Isolation, characterization and antitumour effect on DU145 cells of a main polysaccharide in pollen of chinese wolfberry. Molecules 2018, 23, 2430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Ran, L.; Chen, F.; Zhang, J.; Mi, J.; Lu, L.; Yan, Y.; Cao, Y. Antitumour effects of pollen polysaccharides from Chinese wolfberry on DU145 cells via the PI3K/AKT pathway in vitro and in vivo. Int. J. Biol. Macromol. 2020, 152, 1164–1173. [Google Scholar] [CrossRef] [PubMed]
  44. Chen, D.; Sun, S.; Cai, D.; Kong, G. Induction of mitochondrial-dependent apoptosis in T24 cells by a selenium (Se)-containing polysaccharide from Ginkgo biloba L. leaves. Int. J. Biol. Macromol. 2017, 101, 126–130. [Google Scholar] [CrossRef] [PubMed]
  45. Zhang, F.; Shi, J.-J.; Thakur, K.; Hu, F.; Zhang, J.G.; Wei, Z.J. Anti-cancerous potential of polysaccharide fractions extracted from peony seed dreg on various human cancer cell lines via cell cycle arrest and apoptosis. Front. Pharmacol. 2017, 8, 102. [Google Scholar] [CrossRef] [Green Version]
  46. Hua, Y.; Zhang, J.; Zou, L.; Fu, C.; Li, P.; Zhao, G. Chemical characterization, antioxidant, immune-regulatin and anticancer activities of a novel bioactive polysaccharide from Chenopodium quinoa seeds. Int. J. Biol. Macromol. 2017, 99, 622–629. [Google Scholar] [CrossRef] [PubMed]
  47. Lin, H.-C.; Lin, J.-Y. GSF3, a polysaccharide from guava (Psidium guajava L.) seeds, inhibits MCF-7 breast cancer cell growth via increasing Bax/Bcl-2 ratio or Fas mRNA expression levels. Int. J. Biol. Macromol. 2020, 161, 1261–1271. [Google Scholar] [CrossRef]
  48. Kaya, M.; Sousa, A.G.; Crépeau, M.J.; Sørensen, S.O.; Ralet, M.C. Characterization of citrus pectin samples extracted under different conditions: Influence of acid type and pH of extraction. Ann. Bot. 2014, 114, 1319–1326. [Google Scholar] [CrossRef]
  49. Glinsky, V.V.; Raz, A. Modified citrus pectin anti-metastatic properties: One bullet, multiple targets. Carbohydr. Res. 2009, 344, 1788–1791. [Google Scholar] [CrossRef] [Green Version]
  50. Nangia-Makker, P.; Hogan, V.; Honjo, Y.; Baccarini, S.; Tait, L.; Bresalier, R.; Raz, A. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J. Natl. Cancer Inst. 2002, 94, 1854–1862. [Google Scholar] [CrossRef] [Green Version]
  51. Ahmed, H.; Alsadek, D.M.M. Galectin-3 as a potential target to prevent cancer metastasis. Clin. Med. Insights: Oncol. 2015, 9, 113–121. [Google Scholar] [CrossRef] [PubMed]
  52. Fang, T.; Liu, D.-D.; Ning, H.; Liu, D.; Sun, J.; Huang, X.; Dong, Y.; Geng, M.; Yun, S.; Yan, J.; et al. Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3. Acta Pharmacol. Sin. 2018, 39, 1885–1893. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Wang, S.; Li, P.; Lu, S.M.; Ling, Z.Q. Chemoprevention of low-molecular-weight citrus pectin (LCP) in gastrointestinal cancer cells. Int. J. Biol. Sci. 2016, 12, 746–756. [Google Scholar] [CrossRef] [PubMed]
  54. Conti, S.; Vexler, A.; Hagoel, L.; Kalich-Philosoph, L.; Corn, B.W.; Honig, N.; Shtraus, N.; Meir, Y.; Ron, I.; Eliaz, I.; et al. Modified citrus pectin as a potential sensitizer for radiotherapy in prostate cancer. Integr. Cancer Ther. 2018, 17, 1225–1234. [Google Scholar] [CrossRef] [Green Version]
  55. do Prado, S.B.R.; Shiga, T.M.; Harazono, Y.; Hogan, V.A.; Raz, A.; Carpita, N.C.; Fabi, J.P. Migration and proliferation of cancer cells in culture are differentially affected by molecular size of modified citrus pectin. Carbohydr. Polym. 2019, 211, 141–151. [Google Scholar] [CrossRef]
  56. Pynam, H.; Dharmesh, S.M. A xylorhamnoarabinogalactan I from Bael (Aegle marmelos L.) modulates UV/DMBA induced skin cancer via galectin-3 & gut microbiota. J. Funct. Foods 2019, 60, 103425. [Google Scholar]
  57. do Prado, S.B.R.; Mourão, P.A.S.; Fabi, J.P. Chelate-soluble pectin fraction from papaya pulp interacts with galectin-3 and inhibits colon cancer cell proliferation. Int. J. Biol. Macromol. 2019, 126, 170–178. [Google Scholar] [CrossRef]
  58. Bermudez-Oria, A.; Rodriguez-Gutierrez, G.; Fátima, R.S.; Marta, S.C.; Juan, F.B. Antiproliferative activity of olive extract rich in polyphenols and modified pectin on bladder cancer cells. J. Med. Food 2020, 23, 719–727. [Google Scholar] [CrossRef]
  59. Tanna, B.; Mishra, A. Nutraceutical potential of seaweed polysaccharides: Structure, bioactivity, safety, and toxicity. Compr. Rev. Food Sci. Food Saf. 2019, 18, 817–831. [Google Scholar] [CrossRef] [Green Version]
  60. Zheng, L.-X.; Chen, X.-Q. Current trends in marine algae polysaccharides: The digestive tract, microbial catabolism, and prebiotic potential. Int. J. Biol. Macromol. 2020, 151, 344–354. [Google Scholar] [CrossRef] [PubMed]
  61. Jiao, G.; Yu, G.; Zhang, J.; Ewart, H.S. Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar. Drugs 2011, 9, 196–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Tziveleka, L.-A.; Ioannou, E.; Roussis, V. Ulvan, a bioactive marine sulfated polysaccharide as a key constituent of hybrid biomaterials: A review. Carbohydr. Polym. 2019, 218, 355–370. [Google Scholar] [CrossRef] [PubMed]
  63. Liu, G.; Kuang, S.; Wu, S.; **, W.; Sun, C. A novel polysaccharide from Sargassum integerrimum induces apoptosis in A549 cells and prevents angiogensis in vitro and in vivo. Sci. Rep. 2016, 6, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Vaikundamoorthy, R.; Krishnamoorthy, V.; Vilwanathan, R.; Rajendran, R. Structural characterization and anticancer activity (MCF7 and MDA-MB-231) of polysaccharides fractionated from brown seaweed Sargassum wightii. Int. J. Biol. Macromol. 2018, 111, 1229–1237. [Google Scholar] [CrossRef]
  65. Senthilkumar, K.; Manivasagan, P.; Venkatesan, J.; Kim, S.K. Brown seaweed fucoidan: Biological activity and apoptosis, growth signaling mechanism in cancer. Int. J. Biol. Macromol. 2013, 60, 366–374. [Google Scholar] [CrossRef]
  66. Wang, Z.-J.; Xu, W.; Liang, J.W.; Wang, C.S.; Kang, Y. Effect of fucoidan on B16 murine melanoma cell melanin formation and apoptosis. Afr. J. Tradit. Complement. Altern. Med. 2017, 14, 149–155. [Google Scholar] [CrossRef] [Green Version]
  67. Chen, J.; Hu, Y.; Zhang, L.; Wang, Y.; Wang, S.; Zhang, Y.; Guo, H.; Ji, D.; Wang, Y. Alginate oligosaccharide DP5 exhibits antitumor effects in osteosarcoma patients following surgery. Front. Pharmacol. 2017, 8, 623. [Google Scholar] [CrossRef]
  68. Anand, J.; Sathuvan, M.; Babu, G.V.; Sakthivel, M.; Palani, P.; Nagaraj, S. Bioactive potential and composition analysis of sulfated polysaccharide from Acanthophora spicifera (Vahl) Borgeson. Int. J. Biol. Macromol. 2018, 111, 1238–1244. [Google Scholar] [CrossRef]
  69. Chen, X.; Song, L.; Wang, H.; Liu, S.; Yu, H.; Wang, X.; Li, R.; Liu, T.; Li, P. Partial characterization, the immune modulation and anticancer activities of sulfated polysaccharides from filamentous microalgae tribonema sp. Molecules 2019, 24, 322. [Google Scholar] [CrossRef] [Green Version]
  70. Yang, S.; Wan, H.; Wang, R.; Hao, D. Sulfated polysaccharides from Phaeodactylum tricornutum: Isolation, structural characteristics, and inhibiting HepG2 growth activity in vitro. PeerJ 2019, 7, e6409. [Google Scholar] [CrossRef] [Green Version]
  71. Wanga, H.; Gao, T.; Du, Y.; Yang, H.; Wei, L.; Bi, H.; Ni, W. Anticancer and immunostimulating activities of a novel homogalacturonan from Hippophae rhamnoides L. berry. Carbohydr. Polym. 2015, 131, 288–296. [Google Scholar] [CrossRef] [PubMed]
  72. Han, K.; **, C.; Chen, H.; Wang, P.; Yu, M.; Ding, K. Structural characterization and anti-A549 lung cancer cells bioactivity of a polysaccharide from Houttuynia cordata. Int. J. Biol. Macromol. 2018, 120, 288–296. [Google Scholar] [CrossRef] [PubMed]
  73. Wu, J.; Gao, W.; Song, Z.; **ong, Q.; Xu, Y.; Han, Y.; Yuan, J.; Zhang, R.; Cheng, Y.; Fang, J.; et al. Anticancer activity of polysaccharide from Glehnia littoralis on human lung cancer cell line A549. Int. J. Biol. Macromol. 2018, 106, 464–472. [Google Scholar] [CrossRef] [PubMed]
  74. Zhong, C.; Yang, J.; Lu, Y.; **e, H.; Zhai, S.; Zhang, C.; Luo, Z.; Chen, X.; Fang, X.; Jia, L. Achyranthes bidentata polysaccharide can safely prevent NSCLC metastasis by targeting EGFR and EMT. Signal Transduct. Target. Ther. 2020, 5, 178. [Google Scholar] [CrossRef] [PubMed]
  75. Lina, L.; Wang, P.; Du, Z.; Wang, W.; Cong, Q.; Zheng, C.; **, C.; Ding, K.; Shao, C. Structural elucidation of a pectin from flowers of Lonicera japonica and its antipancreatic cancer activity. Int. J. Biol. Macromol. 2016, 88, 130–137. [Google Scholar] [CrossRef]
  76. Zhanga, S.; He, F.; Chen, X.; Ding, K. Isolation and structural characterization of a pectin from Lycium ruthenicum Murr and its anti-pancreatic ductal adenocarcinoma cell activity. Carbohydr. Polym. 2019, 223, 115104. [Google Scholar] [CrossRef]
  77. Xu, L.; Cao, J.; Chen, W. Structural characterization of a broccoli polysaccharide and evaluation of anticancer cell proliferation effects. Carbohydr. Polym. 2015, 126, 179–184. [Google Scholar] [CrossRef]
  78. Zhang, Z.F.; Lv, G.Y.; Jiang, X.; Cheng, J.H.; Fan, L.F. Extraction optimization and biological properties of a polysaccharide isolated from Gleoestereum incarnatum. Carbohydr. Polym. 2015, 117, 185–191. [Google Scholar] [CrossRef]
  79. Wang, Y.; Liu, X.; Zhang, J.; Liu, G.; Liu, Y.; Wang, K.; Yang, M.; Cheng, H.; Zhao, Z. Structural characterization and in vitro antitumour activity of polysaccharides from Zizyphus jujuba cv. Muzao. RSC Adv. 2015, 5, 7860–7867. [Google Scholar] [CrossRef]
  80. Zhao, C.; Li, Z.; Li, C.; Yang, L.; Yao, L.; Fu, Y.; He, X.; Shi, K.; Lu, Z. Optimized extraction of polysaccharides from Taxus chinensis var. mairei fruits and its antitumour activity. Int. J. Biol. Macromol. 2015, 75, 192–198. [Google Scholar] [CrossRef]
  81. Feng, Y.-N.; Zhang, X.-F. Polysaccharide extracted from Huperzia serrata using response surface methodology and its biological activity. Int. J. Biol. Macromol. 2020, 157, 267–275. [Google Scholar] [CrossRef] [PubMed]
  82. Ren, F.; Li, J.; Yuan, X.; Wang, Y.; Wu, K.; Kang, L.; Luo, Y.; Zhang, H.; Yuan, Z. Dandelion polysaccharides exert anticancer effect on Hepatocellular carcinoma by inhibiting PI3K/AKT/mTOR pathway and enhancing immune response. J. Funct. Foods 2019, 55, 263–274. [Google Scholar] [CrossRef]
  83. Ren, F.; Wu, K.; Yang, Y.; Yang, Y.; Wang, Y.; Li, J. Dandelion polysaccharide exerts anti-angiogenesis effect on hepatocellular carcinoma by regulating VEGF/HIF-1a expression. Front. Pharmacol. 2020, 11, 460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Wang, J.-H.; Luo, J.-P. Comparison of antitumor activities of different polysaccharide fractions from the stems of Dendrobium nobile Lindl. Carbohydr. Polym. 2010, 79, 114–118. [Google Scholar] [CrossRef]
  85. Yeung, B.K.S.; Chong, P.Y.C.; Petillo, P.A. Synthesis of Glycosaminoglycans. J. Carbohydr. Chem. 2002, 21, 799–865. [Google Scholar] [CrossRef]
  86. Pomin, V.H.; Mulloy, B. Glycosaminoglycans and proteoglycans. Pharmaceuticals 2018, 11, 27. [Google Scholar] [CrossRef] [Green Version]
  87. Mende, M.; Bednarek, C.; Wawryszyn, M.; Sauter, P.; Biskup, M.B.; Schepers, U.; Bräse, S. Chemical synthesis of glycosaminoglycans. Chem. Rev. 2016, 116, 8193–8255. [Google Scholar] [CrossRef]
  88. Volpi, N. Therapeutic applications of glycosaminoglycans. Curr. Med. Chem. 2006, 13, 1799–1810. [Google Scholar] [CrossRef]
  89. Berdiaki, A.; Neagu, M.; Giatagana, E.M.; Kuskov, A.; Tsatsakis, A.M.; Tzanakakis, G.N.; Nikitovic, D. Glycosaminoglycans: Carriers and Targets for Tailored Anti-Cancer Therapy. Biomolecules 2021, 11, 395. [Google Scholar] [CrossRef]
  90. Li, W.; Johnson, D.J.D.; Esmon, C.T.; Huntington, J.A. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat. Struct. Mol. Biol. 2004, 11, 857–862. [Google Scholar] [CrossRef]
  91. Khorana, A.A.; Streiff, M.B.; Farge, D.; Mandala, M.; Debourdeau, P.; Cajfinger, F.; Marty, M.; Falanga, A.; Lyman, G.H. Venous thromboembolism prophylaxis and treatment in cancer: A consensus statement of major guidelines panels and call to action. J. Clin. Oncol. 2009, 27, 4919–4926. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  92. Farge, D.; Bounameaux, H.; Brenner, B.; Cajfinger, F.; Debourdeau, P.; Khorana, A.A.; Pabinger, I.; Solymoss, S.; Douketis, J.; Kakkar, A. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016, 17, e452–e466. [Google Scholar] [CrossRef]
  93. Frere, C.; Benzidia, I.; Marjanovic, Z.; Farge, D. Recent advances in the management of cancer-associated thrombosis: New Hopes but New Challenges. Cancers 2019, 11, 71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Gil-Bernabé, A.M.; Lucotti, S.; Muschel, R.J. Coagulation and metastasis: What does the experimental literature tell us? Br. J. Haematol. 2013, 162, 433–441. [Google Scholar] [CrossRef] [Green Version]
  95. Walenga, J.M.; Lyman, G.H. Evolution of heparin anticoagulants to ultralow-molecular-weight heparins: A review of pharmacologic and clinical differences and applications in patients with cancer. Crit. Rev. Oncol. Hematol. 2013, 88, 1–18. [Google Scholar] [CrossRef]
  96. Zhang, W.; Swanson, R.; Izaguirre, G.; **ong, Y.; Lau, L.F.; Olson, S.T. The heparin-binding site of antithrombin is crucial for antiangiogenic activity. Blood 2005, 106, 1621–1628. [Google Scholar] [CrossRef] [Green Version]
  97. Rohloff, J.; Zinke, J.; Schoppmeyer, K.; Tannapfel, A.; Witzigmann, H.; Mössner, J.; Wittekind, C.; Caca, K. Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma. Br. J. Cancer 2002, 86, 1270–1275. [Google Scholar] [CrossRef]
  98. Ludwig, R.J.; Boehme, B.; Podda, M.; Henschler, R.; Jager, E.; Tandi, C.; Boehncke, W.H.; Zollner, T.M.; Kaufmann, R.; Gille, J. Endothelial P-selectin as a target of heparin action in experimental melanoma lung metastasis. Cancer Res. 2004, 64, 2743–2750. [Google Scholar] [CrossRef] [Green Version]
  99. Hwang, H.H.; Jeong, H.J.; Yun, S.; Byun, Y.; Okano, T.; Kim, S.W.; Lee, D.Y. Anticancer effect of heparin–taurocholate conjugate on orthotopically induced exocrine and endocrine pancreatic cancer. Cancers 2021, 13, 5775. [Google Scholar] [CrossRef]
  100. Kim, J.-y.; Al-Hilal, T.A.; Chung, S.W.; Kim, S.Y.; Ryu, G.H.; Son, W.C.; Byun, Y. Antiangiogenic and anticancer effect of an orally active low molecular weight heparin conjugates and its application to lung cancer chemoprevention. J. Control. Release 2015, 199, 122–131. [Google Scholar] [CrossRef]
  101. Pfankuchena, D.B.; Stölting, D.P.; Schlesinger, M.; Royer, H.D.; Bendas, G. Low molecular weight heparin tinzaparin antagonizes cisplatin resistance of ovarian cancer cells. Biochem. Pharmacol. 2015, 97, 147–157. [Google Scholar] [CrossRef] [PubMed]
  102. Park, J.; Jeong, J.-H.; Al-Hilal, T.A.; Kim, J.; Byun, Y. Size controlled heparin fragment−deoxycholic acid conjugate showed anticancer property by inhibiting VEGF165. Bioconjugate Chem. 2015, 26, 932–940. [Google Scholar] [CrossRef] [PubMed]
  103. Park, J.; Kim, J.-y.; Hwang, S.R.; Mahmud, F.; Byun, Y. Chemical conjugate of low molecular weight heparin and suramin fragment inhibits tumor growth possibly by blocking VEGF165. Mol. Pharm. 2015, 12, 3935–3942. [Google Scholar] [CrossRef]
  104. Parka, J.; Hwang, S.R.; Choi, J.U.; Alam, F.; Byun, Y. Self-assembled nanocomplex of PEGylated protamine and heparin–suramin conjugate for accumulation at the tumor site. Int. J. Pharm. 2018, 535, 38–46. [Google Scholar] [CrossRef]
  105. Yang, Y.-C.; Cai, J.; Yin, J.; Zhang, J.; Wang, K.L.; Zhang, Z.T. Heparin-functionalized Pluronic nanoparticles to enhance the antitumour efficacy of sorafenib in gastric cancers. Carbohydr. Polym. 2016, 136, 782–790. [Google Scholar] [CrossRef]
  106. Seib, F.P.; Tsurkan, M.; Freudenberg, U.; Kaplan, D.L.; Werner, C. Heparin-modified polyethylene glycol microparticle aggregates for focal cancer chemotherapy. ACS Biomater. Sci. Eng. 2016, 2, 2287–2293. [Google Scholar] [CrossRef] [Green Version]
  107. Li, J.; Pan, H.; Qiao, S.; Li, Y.; Wang, J.; Liu, W.; Pan, W. The utilization of lowmolecular weight heparin-poloxamer associated Laponite nanoplatform for safe and efficient tumor therapy. Int. J. Biol. Macromol. 2019, 134, 63–72. [Google Scholar] [CrossRef]
  108. Newlanda, B.; Varricchio, C.; Körner, Y.; Hoppe, F.; Taplan, C.; Newland, H.; Eigel, D.; Tornillo, G.; Pette, D.; Brancale, A.; et al. Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis. Carbohydr. Polym. 2020, 245, 116504. [Google Scholar] [CrossRef] [PubMed]
  109. Wang, D.; Luo, W.; Wen, G.; Yang, L.; Hong, S.; Zhang, S.; Diao, J.; Wang, J.; Wei, H.; Li, Y.; et al. Synergistic effects of negatively charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells. Ultrason. Sonochem. 2017, 34, 448–457. [Google Scholar] [CrossRef] [PubMed]
  110. Tian, F.; Dahmani, F.Z.; Qiao, J.; Ni, J.; **ong, H.; Liu, T.; Zhou, J.; Yao, J. A targeted nanoplatform codelivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer. Acta Biomater. 2018, 75, 398–412. [Google Scholar] [CrossRef]
  111. Thi, T.T.H.; Tran, D.-H.N.; Bach, L.G.; Vu-Quang, H.; Nguyen, D.C.; Park, K.D.; Nguyen, D.H. Functional magnetic core-shell system-based iron oxide nanoparticle coated with biocompatible copolymer for anticancer drug delivery. Pharmaceutics 2019, 11, 120. [Google Scholar]
  112. Qiu, L.; Ge, L.; Long, M.; Mao, J.; Ahmed, K.S.; Shan, X.; Zhang, H.; Qin, L.; Lv, G.; Chen, J. Redox-responsive biocompatible nanocarriers based on novel heparosan polysaccharides for intracellular anticancer drug delivery. Asian J. Pharm. Sci. 2020, 15, 83–94. [Google Scholar] [CrossRef] [PubMed]
  113. Guo, R.; Long, Y.; Lu, Z.; Deng, M.; He, P.; Li, M.; He, Q. Enhanced stability and efficacy of GEM-TOS prodrug by coassembly with antimetastatic shell LMWH-TOS. Acta Pharm. Sin. B 2020, 10, 1977–1988. [Google Scholar] [CrossRef] [PubMed]
  114. Trana, T.H.; Bae, B.-c.; Lee, Y.; Na, K.; Huh, K.M. Heparin-folate-retinoic acid bioconjugates for targeted delivery of hydrophobic photosensitizers. Carbohydr. Polym. 2013, 92, 1615–1624. [Google Scholar] [CrossRef] [PubMed]
  115. Shi, X.; Wang, Y.; Sun, H.; Chen, Y.; Zhang, X.; Xu, J.; Zhai, G. Heparin-reduced graphene oxide nanocomposites for curcumin delivery: In vitro, in vivo and molecular dynamics simulation study. Biomater. Sci. 2019, 7, 1011. [Google Scholar] [CrossRef] [PubMed]
  116. Wu, Y.; Li, F.; Zhang, X.; Li, Z.; Zhang, Q.; Wang, W.; Pan, D.; Zheng, X.; Gu, Z.; Zhang, H.; et al. Tumor microenvironment-responsive PEGylated heparin-pyropheophorbide-a nanoconjugates for photodynamic therapy. Carbohydr. Polym. 2021, 255, 117490. [Google Scholar] [CrossRef]
  117. Chaudhry, G.-e.S.; Akim, A.; Zafar, M.N.; Safdar, N.; Sung, Y.Y.; Muhammad, T.S.T. Understanding hyaluronan receptor (CD44) interaction, HA-CD44 activated potential targets in cancer therapeutics. Adv. Pharm. Bull. 2021, 11, 426–438. [Google Scholar] [CrossRef]
  118. Dosio, F.; Arpicco, S.; Stella, B.; Fattal, E. Hyaluronic acid for anticancer drug and nucleic acid delivery. Adv. Drug Deliv. Rev. 2016, 97, 204–236. [Google Scholar] [CrossRef]
  119. Espejo-Román, J.M.; Rubio-Ruiz, B.; Cano-Cortés, V.; Cruz-López, O.; Gonzalez-Resines, S.; Domene, C.; Conejo-García, A.; Sánchez-Martín, R.M. Selective anticancer therapy based on a HA-CD44 interaction inhibitor loaded on polymeric nanoparticles. Pharmaceutics 2022, 14, 788. [Google Scholar] [CrossRef]
  120. Mo, Y.; Wang, H.; Liu, J.; Lan, Y.; Guo, R.; Zhang, Y.; Xue, W.; Zhang, Y. Controlled release and targeted delivery to cancer cells of doxorubicin from polysaccharide-functionalised single-walled carbon nanotubes. J. Mater. Chem. B 2015, 3, 1846–1855. [Google Scholar] [CrossRef]
  121. Chen, W.; Wang, F.; Zhang, X.; Hu, J.; Wang, X.; Yang, K.; Huang, L.; Xu, M.; Li, Q.; Fu, L. Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan-drug nanocomplex. J. Mater. Chem. B 2016, 4, 6652–6661. [Google Scholar] [CrossRef] [PubMed]
  122. Teong, B.; Lin, C.-Y.; Chang, S.J.; Niu, G.C.C.; Yao, C.H.; Chen, I.F.; Kuo, S.M. Enhanced anticancer activity by curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells. J. Mater. Sci. Mater. Med. 2015, 26, 1–15. [Google Scholar] [CrossRef] [PubMed]
  123. Hsiao, K.Y.; Wu, Y.-J.; Liu, Z.; Chuang, C.; Huang, H.; Kuo, S. Anticancer effects of sinulariolide-conjugated hyaluronan nanoparticles on lung adenocarcinoma cells. Molecules 2016, 21, 297. [Google Scholar] [CrossRef] [PubMed]
  124. Chen, D.; Dong, X.; Qi, M.; Song, X.; Sun, J. Dual pH/redox responsive and CD44 receptor targeting hybrid nanochrysalis based on new oligosaccharides of hyaluronan conjugates. Carbohydr. Polym. 2017, 157, 1272–1280. [Google Scholar] [CrossRef]
  125. Cai, Z.; Zhang, H.; Wei, Y.; Wei, Y.; **e, Y.; Cong, F. Reduction- and pH-sensitive hyaluronan nanoparticles for delivery of iridium(III) anticancer drugs. Biomacromolecules 2017, 18, 2102–2117. [Google Scholar] [CrossRef]
  126. Zhang, W.; Tung, C.-H. Redox-responsive cisplatin nanogels for anticancer drug Delivery. Chem. Commun. 2018, 54, 8367–8370. [Google Scholar] [CrossRef] [PubMed]
  127. Sun, Z.; Yi, Z.; Cui, X.; Chen, X.; Su, W.; Ren, X.; Li, X. Tumor-targeted and nitric oxide-generated nanogels of keratin and hyaluronan for enhanced cancer therapy. Nanoscale 2018, 10, 12109–12122. [Google Scholar] [CrossRef]
  128. Amano, Y.; Ohta, S.; Sakura, K.L.; Ito, T. Pemetrexed-conjugated hyaluronan for the treatment of malignant pleural mesothelioma. Eur. J. Pharm. Sci. 2019, 138, 105008. [Google Scholar] [CrossRef]
  129. Yu, J.S.; Shin, D.H.; Kim, J.S. Repurposing of fluvastatin as an anticancer agent against breast cancer stem cells via encapsulation in a hyaluronan-conjugated liposome. Pharmaceutics 2020, 12, 1133. [Google Scholar] [CrossRef]
  130. Kang, Y.; Sun, W.; Li, S.; Li, M.; Fan, J.; Du, J.; Liang, X.J.; Peng, X. Oligo Hyaluronan-Coated Silica/Hydroxyapatite Degradable Nanoparticles for Targeted Cancer Treatment. Adv. Sci. 2019, 6, 1–11. [Google Scholar] [CrossRef] [Green Version]
  131. Cosco, D.; Mare, R.; Paolino, D.; Salvatici, M.C.; Cilurzo, F.; Fresta, M. Sclareol-loaded hyaluronan-coated PLGA nanoparticles: Physico-chemical properties and in vitro anticancer features. Int. J. Biol. Macromol. 2019, 132, 550–557. [Google Scholar] [CrossRef] [PubMed]
  132. Wang, J.; Muhammad, N.; Li, T.; Wang, H.; Liu, Y.; Liu, B.; Zhan, H. Hyaluronic acid-coated camptothecin nanocrystals for targeted drug delivery to enhance anticancer efficacy. Mol. Pharm. 2020, 17, 2411–2425. [Google Scholar] [CrossRef] [PubMed]
  133. Yang, H.; Miao, Y.; Chen, L.; Li, Z.; Yang, R.; Xu, X.; Liu, Z.; Zhang, L.M.; Jiang, X. Redox-responsive nanoparticles from disulfide bond-linked poly-(N-ε-carbobenzyloxy-L-lysine)-grafted hyaluronan copolymers as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Int. J. Biol. Macromol. 2020, 148, 483–492. [Google Scholar] [CrossRef] [PubMed]
  134. Poudel, K.; Gautam, M.; Maharjan, S.; Jeong, J.H.; Choi, H.G.; Khan, G.M.; Yong, C.S.; Kim, J.O. Dual stimuli-responsive ursolic acid-embedded nanophytoliposome for targeted antitumour therapy. Int. J. Pharm. 2020, 582, 119330. [Google Scholar] [CrossRef]
  135. Cong, Z.; Zhang, L.; Ma, S.Q.; Lam, K.S.; Yang, F.F.; Liao, Y.H. Size-transformable hyaluronan stacked self-assembling peptide nanoparticles for improved transcellular tumor penetration and photo−chemo combination therapy. ACS Nano 2020, 14, 1958–1970. [Google Scholar] [CrossRef]
  136. Gao, X.; Wei, M.; Ma, D.; Yang, X.; Zhang, Y.; Zhou, X.; Li, L.; Deng, Y.; Yang, W. Engineering of a hollow-structured Cu2−XS nano-homojunction platform for near infrared-triggered infected wound healing and cancer therapy. Adv. Funct. Mater. 2021, 31, 2106700. [Google Scholar] [CrossRef]
  137. Gao, S.; Islam, R.; Fang, J. Tumor environment-responsive hyaluronan conjugated zinc protoporphyrin for targeted anticancer photodynamic therapy. J. Pers. Med. 2021, 11, 136. [Google Scholar] [CrossRef]
  138. Kim, J.-E.; Park, Y.-J. Hyaluronan self-agglomerating nanoparticles for non-small cell lung cancer targeting. Cancer Nanotechnol. 2022, 13, 1–24. [Google Scholar] [CrossRef]
  139. Chang, Y.-L.; Liao, P.B.; Wu, P.H.; Chang, W.J.; Lee, S.Y.; Huang, H.M. Cancer cytotoxicity of a hybrid hyaluronan-superparamagnetic iron oxide nanoparticle material: An in-vitro evaluation. Nanomaterials 2022, 12, 496. [Google Scholar] [CrossRef]
  140. Jacquinet, J.C.; Lopin-Bon, C.; Vibert, A. From polymer to size-defined oligomers: A highly divergent and stereocontrolled construction of chondroitin sulfate A, C, D, E, K, L, and M oligomers from a single precursor: Part 2. Chem. Eur. 2009, 15, 9579–9595. [Google Scholar] [CrossRef]
  141. Jardim, K.V.; Joanitti, G.A.; Azevedo, R.B.; Parize, A.L. Physico-chemical characterization and cytotoxicity evaluation of curcumin loaded in chitosan/chondroitin sulfate nanoparticles. Mater. Sci. Eng. C 2015, 56, 294–304. [Google Scholar] [CrossRef] [PubMed]
  142. Bárbara, S.; Cátia, C.; Nunes, S.; Panice, M.R.; Scariot, D.B.; Nakamura, C.V.; Muniz, E.C. Manufacturing micro/nano chitosan/chondroitin sulfate curcumin-loaded hydrogel in ionic liquid: A new biomaterial effective against cancer cells. Int. J. Biol. Macromol. 2021, 180, 88–96. [Google Scholar]
  143. Yuan, Y.; Ma, M.; Zhang, S.; Liu, C.; Chen, P.; Li, H.; Wang, D.; Xu, Y. Effect of sophorolipid on the curcumin-loaded ternary composite nanoparticles self-assembled from zein and chondroitin sulfate. Food Hydrocoll. 2021, 113, 106493. [Google Scholar] [CrossRef]
  144. Soe, Z.C.; Poudel, B.K.; Nguyen, H.T.; Thapa, R.K.; Ou, W.; Gautam, M.; Poudel, K.; **, S.G.; Jeong, J.H.; Ku, S.K.; et al. Folate-targeted nanostructured chitosan/chondroitin sulfate complex carriers for enhanced delivery of bortezomib to colorectal cancer cells. Asian J. Pharm. Sci. 2019, 14, 40–51. [Google Scholar] [CrossRef] [PubMed]
  145. Liang, T.; Zhang, Z.; **g, P. Black rice anthocyanins embedded in self-assembled chitosan/chondroitin sulfate nanoparticles enhance apoptosis in HCT-116 cells. Food Chem. 2019, 301, 125280. [Google Scholar] [CrossRef] [PubMed]
  146. Barkat, K.; Ahmad, M.; Minhas, M.U.; Khalid, I.; Malik, N.S. Chondroitin sulfate-based smart hydrogels for targeted delivery of oxaliplatin in colorectal cancer: Preparation, characterization and toxicity evaluation. Polym. Bull. 2020, 77, 6271–6297. [Google Scholar] [CrossRef]
  147. Li, M.; Sun, J.; Zhang, W.; Zhao, Y.; Zhang, S.; Zhang, S. Drug delivery systems based on CD44-targeted glycosaminoglycans for cancer therapy. Carbohydr. Polym. 2021, 251, 117103. [Google Scholar] [CrossRef]
  148. Zu, M.; Ma, L.; Zhang, X.; **e, D.; Kang, Y.; **ao, B. Chondroitin sulfate-functionalized polymeric nanoparticles for colon cancer-targeted chemotherapy. Colloids Surf. B: Biointerfaces 2019, 177, 399–406. [Google Scholar] [CrossRef]
  149. Chen, Y.; Li, B.; Chen, X.; Wu, M.; Ji, Y.; Tang, G.; **, Y. A supramolecular codelivery strategy for combined breast cancer treatment and metastasis prevention. Chin. Chem. Lett. 2020, 31, 1153–1158. [Google Scholar] [CrossRef]
  150. Singhai, N.J.; Maheshwari, R.; Jain, N.K.; Ramteke, S. Chondroitin sulfate and α-tocopheryl succinate tethered multiwalled carbon nanotubes for dual-action therapy of triple-negative breast cancer. J. Drug Deliv. Sci. Technol. 2020, 60, 102080. [Google Scholar] [CrossRef]
  151. Zhang, Z.; Ma, L.; Luo, J. Chondroitin sulfate-modified liposomes for targeted co-delivery of doxorubicin and retinoic acid to suppress breast cancer lung metastasis. Pharmaceutics 2021, 13, 406. [Google Scholar] [CrossRef] [PubMed]
  152. Shi, X.; Yang, X.; Liu, M.; Wang, R.; Qiu, N.; Liu, Y.; Yang, H.; Ji, J.; Zhai, G. Chondroitin sulfate-based nanoparticles for enhanced chemo-photodynamic therapy overcoming multidrug resistance and lung metastasis of breast cancer. Carbohydr. Polym. 2021, 254, 117459. [Google Scholar] [CrossRef] [PubMed]
  153. Wu, R.; Shang, N.; Gui, M.; Yin, J.; Li, P. Sturgeon (acipenser)-derived chondroitin sulfate suppresses human colon cancer HCT-116 both in vitro and in vivo by inhibiting proliferation and inducing apoptosis. Nutrients 2020, 12, 1130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  154. Peng, C.; Wang, Q.; Jiao, R.; Xu, Y.; Han, N.; Wang, W.; Zhu, C.; Li, F. A novel chondroitin sulfate E from Dosidicus gigas cartilage and its antitumour metastatic activity. Carbohydr. Polym. 2021, 262, 117971. [Google Scholar] [CrossRef]
  155. Thinh, P.D.; Ly, B.M.; Usoltseva, R.V.; Shevchenko, N.M.; Rasin, A.B.; Anastyuk, S.D.; Malyarenko, O.S.; Zvyagintseva, T.N.; San, P.T.; Ermakova, S.P. A novel sulfated fucan from Vietnamese sea cucumber Stichopus variegatus: Isolation, structure and anticancer activity in vitro. Int. J. Biol. Macromol. 2018, 117, 1101–1109. [Google Scholar] [CrossRef]
  156. Aldairi, A.F.; Ogundipe, O.D.; Pye, D.A. Antiproliferative Activity of Glycosaminoglycan-Like Polysaccharides Derived from Marine Molluscs. Mar. Drugs 2018, 16, 63. [Google Scholar] [CrossRef] [Green Version]
  157. Sasaki, T.; Takasuka, N. Further Study of the Structure of Lentinan, an Antitumour Polysaccharide from Lentinus Edodes. Carbohydr. Res. 1976, 47, 99–104. [Google Scholar] [CrossRef]
  158. Chen, Q.; Zheng, Y.; Chen, X.; Ge, P.; Wang, P.; Wu, B. Upregulation of miR-216a-5p by lentinan targeted inhibition of JAK2/STAT3 signaling pathway to reduce lung adenocarcinoma cell stemness, promote apoptosis, and slow down the lung adenocarcinoma, mechanisms. Front. Oncol. 2021, 11, 778096. [Google Scholar] [CrossRef]
  159. Liu, Z.; Yu, L.; Gu, P.; Bo, R. Preparation of lentinan-calcium carbonate microspheres and their application as vaccine adjuvants. Carbohydr. Polym. 2020, 245, 116520. [Google Scholar] [CrossRef]
  160. Yang, F.; Huang, J.; Liu, H.; Lin, W.; Li, X.; Zhu, X.; Chen, T. Lentinan-functionalized selenium nanosystems with high permeability infiltrate solid tumors by enhancing transcellular transport. Nanoscale 2020, 12, 14494–14503. [Google Scholar] [CrossRef]
  161. Song, Z.; Luo, W.; Zheng, H.; Zeng, Y.; Wang, J.; Chen, T. Translational nanotherapeutics reprograms immune microenvironment in malignant pleural effusion of lung adenocarcinoma. Adv. Healthc. Mater. 2021, 10, 2100149. [Google Scholar] [CrossRef]
  162. Lu, J.; He, R.; Sun, P.; Zhang, F.; Linhardt, R.J. Molecular mechanisms of bioactive polysaccharides from Ganoderma lucidum (Lingzhi). a review. Int. J. Biol. Macromol. 2020, 150, 765–774. [Google Scholar] [CrossRef] [PubMed]
  163. Dong, Q.; Wang, Y.; Shi, L.; Yao, J.; Li, J.; Ma, F.; Ding, K. A novel water-soluble β-D-glucan isolated from the spores of Ganoderma lucidum. Carbohydr. Res. 2012, 353, 100–105. [Google Scholar] [CrossRef] [PubMed]
  164. Bao, X.-F.; Zhen, Y.; Ruan, L.; Fang, J.N. Purification, characterization, and modification of T lymphocyte-stimulating polysaccharide from spores of Ganoderma lucidum. Chem. Pharm. Bull. 2002, 50, 623–629. [Google Scholar] [CrossRef] [PubMed]
  165. Fu, Y.; Shi, L.; Ding, K. Structure elucidation and antitumour activity in vivo of a polysaccharide from spores of Ganoderma lucidum (Fr.) Karst. Int. J. Biol. Macromol. 2019, 141, 693–699. [Google Scholar] [CrossRef]
  166. Liu, H.; Amakye, W.K.; Ren, J. Codonopsis pilosula polysaccharide in synergy with dacarbazine inhibits mouse melanoma by repolarizing M2-like tumor-associated macrophages into M1-like tumor-associated macrophages. Biomed. Pharmacother. 2021, 142, 112016. [Google Scholar] [CrossRef]
  167. da Silva Milhorini, S.; de Lima Bellan, D.; Zavadinack, M.; Simas, F.F.; Smiderle, F.R.; de Santana-Filho, A.P.; Sassaki, G.L.; Iacomini, M. Antimelanoma effect of a fucoxylomannan isolated from Ganoderma lucidum fruiting bodies. Carbohydr. Polym. 2022, 294, 119823. [Google Scholar] [CrossRef] [PubMed]
  168. Hsu, W.-H.; Qiu, W.-L.; Tsao, S.M.; Tseng, A.J.; Lu, M.K.; Hua, W.J.; Cheng, H.C.; Hsu, H.Y.; Lin, T.Y. Effects ofWSG, a polysaccharide from Ganoderma lucidum, on suppressing cell growth and mobility of lung cancer. Int. J. Biol. Macromol. 2020, 165, 1604–1613. [Google Scholar] [CrossRef]
  169. Hsu, W.-H.; Hua, W.-J.; Qiu, W.L.; Tseng, A.J.; Cheng, H.C.; Lin, T.Y. WSG, a glucose-enriched polysaccharide from Ganoderma lucidum, suppresses tongue cancer cells via inhibition of EGFR-mediated signaling and potentiates cisplatin-induced apoptosis. Int. J. Biol. Macromol. 2021, 193, 1201–1208. [Google Scholar] [CrossRef]
  170. Zhang, S.; Pang, G.; Chen, C.; Qin, J.; Yu, H.; Liu, Y.; Zhang, X.; Song, Z.; Zhao, J.; Wang, F.; et al. Effective cancer immunotherapy by Ganoderma lucidum polysaccharide-gold nanocomposites through dendritic cell activation and memory T-cell response. Carbohydr. Polym. 2019, 205, 192–202. [Google Scholar] [CrossRef]
  171. Yu, H.; Yang, Y.; Jiang, T.; Zhang, X.; Zhao, Y.; Pang, G.; Feng, Y.; Zhang, S.; Wang, F.; Wang, Y.; et al. Effective Radiotherapy in Tumor Assisted by Ganoderma lucidum Polysaccharide-Conjugated Bismuth Sulfide Nanoparticles through Radiosensitization and Dendritic Cell Activation. ACS Appl. Mater. Interfaces 2019, 11, 27536–27547. [Google Scholar] [CrossRef] [PubMed]
  172. Soerjomataram, I.; Bray, F. Planning for tomorrow: Global cancer incidence and the role of prevention 2020–2070. Nat. Rev. Clin. Oncol. 2021, 18, 663–672. [Google Scholar] [CrossRef] [PubMed]
Molecules 27 08083 g001 550
Figure 1. The major MAP in red seaweed (A), brown seaweed (B), and green seaweed (C).
Figure 1. The major MAP in red seaweed (A), brown seaweed (B), and green seaweed (C).
Molecules 27 08083 g001
Molecules 27 08083 g002 550
Figure 2. Four classes of mammalian GAGs and their potential sulfation sites. (A) (HP)/heparan sulfate (HS), (B) Hyaluronan (HA), (C) Chondroitin sulfate (CS)/Dermatan sulfate (DS), and (D) Keratan sulfate (KS).
Figure 2. Four classes of mammalian GAGs and their potential sulfation sites. (A) (HP)/heparan sulfate (HS), (B) Hyaluronan (HA), (C) Chondroitin sulfate (CS)/Dermatan sulfate (DS), and (D) Keratan sulfate (KS).
Molecules 27 08083 g002
Molecules 27 08083 g003 550
Figure 3. Mechanism of action of HA-based drug delivery targeting CD44.
Figure 3. Mechanism of action of HA-based drug delivery targeting CD44.
Molecules 27 08083 g003
Molecules 27 08083 g004 550
Figure 4. The repeating unit of the LNT structure.
Figure 4. The repeating unit of the LNT structure.
Molecules 27 08083 g004
Molecules 27 08083 g005 550
Figure 5. The mechanism action of the Lentinan.
Figure 5. The mechanism action of the Lentinan.
Molecules 27 08083 g005
Molecules 27 08083 g006 550
Figure 6. The structures of GLPs. (A) GLSA50-1B, (B) PSGL-I-1A, (C) WGLP.
Figure 6. The structures of GLPs. (A) GLSA50-1B, (B) PSGL-I-1A, (C) WGLP.
Molecules 27 08083 g006
Table
Table 1. Performance and structural features of natural anticancer polysaccharides.
Table 1. Performance and structural features of natural anticancer polysaccharides.
Natural PolysaccharidesPerformancesStructural Features
Polysaccharides from plantsTarget Twist/AKR1C2/NF-1 pathwayacidic protein–polysaccharide
Polysaccharides from animalsAntiangiogenic propertiesGlcN-GlcA or GlcN-IdoA
Polysaccharides from fungiInhibiting JAK2/STAT3 signaling pathwayβ-(1→3) glucose linkages
Table
Table 2. Ginseng polysaccharides with antitumour activity.
Table 2. Ginseng polysaccharides with antitumour activity.
CompoundStructure FeaturesMWAntitumor MechanismRef.
PGPW197.4% carbohydrate and 1.2% uronic acid~3.5 × 105 DaNot been elucidated[14,15]
PGP2aAcidic protein–polysaccharide~3.2 × 104 DaTarget Twist/AKR1C2/NF-1 pathway[16]
RG-IRG-I and side chains AG-I~6 × 104 DaBound to galectin-3[17]
MCGP-1The ratio of Rha/GalA is 0.821.649 × 105 DaMight be related to the Ara residues linked to the surface of the polysaccharide[18]
MCGP-2Mainly composed of GalA, Ara, Gal, Rha, and Glc1.644 × 105 DaThe same mechanism as MCGP-1[18]
MCGP-3The characteristic compositions of RG-I pectin1.572 × 105 DaThe same mechanism as MCGP-1 and contains disaccharide [-(1, 4)-α-D-GalAp-(1, 2. -α-L-Rhap-][18]
MCGP-4The characteristic compositions of RG-I pectin1.673 × 105 DaThe same mechanism as MCGP-1[18]
MCGP-5The ratio of Rha/GalA is 0.241.600 × 105 DaThe same mechanism as MCGP-1[18]
MCGP-6Mainly composed of GalA, Ara, Gal, Rha, and Glc1.592 × 105 DaThe same mechanism as MCGP-1[18]
MCGP-7Mainly composed of GalA, Ara, Gal, Rha, and Glc1.520 × 105 DaThe same mechanism as MCGP-1[18]
Table
Table 3. Seeds’ polysaccharides with anticancer activity.
Table 3. Seeds’ polysaccharides with anticancer activity.
Plants SpeciesTypes of Carcinoma Cell LinesRef.
Peony seedsPc-3/HCT-116/MCF-7/Hela[45]
Chenopodium quinoa seedsSMMC 7721/MCF-7[46]
Psidium guajava L. seedsMCF-7[47]
Table
Table 4. Polysaccharides from other species of plants with antitumour activity.
Table 4. Polysaccharides from other species of plants with antitumour activity.
Plants Species Structure FeaturesTypes of Carcinoma Cell LinesRef.
BroccoliComprised of Ara, Gal, and Rha with a molar ratio of 5.3:0.8:1.0HepG2, Siha cervical, MDA-MB-231[77]
Gleoestereum incarnatumComposed of Gal, Glc, xylose, and Man at molar ratios of 1:4.25:1.14:1.85HepG2[78]
Zizyphus jujuba cv.MuzaoPresence of RG-I domains and typical pectic polysaccharides, with homogalacturonan (methyl and acetyl esterified)HepG2[79]
Taxus chinensis var.mairei fruits S180[80]
Huperzia serrataComposed of Gal, Glc, Ara, Rha, Man, GalA, and so onSkov3 and A2780[81]
Dandelionα-type polysaccharides, consisted of Glc, Gal, Ara, arabinose rhamnose, and GlcAHepG2[82,83]
Dendrobium nobile LindlComposed of Gal, Glc, Ara, Rha, Man, and so onSarcoma 180[84]
Table
Table 5. Application of HP in antitumour therapy.
Table 5. Application of HP in antitumour therapy.
CompoundHP Combination TypesAnticancer MechanismsTypes of CancerRef.
LHTHP–drug conjugateAntiangiogenic propertiesPancreatic cancer cells-bearing mice[99]
Oral LMWH conjugate (LHTD4)HP–drug conjugateAntiangiogenic propertiesA549 lung cancer cells[100]
Tinzaparin, a LMWHHP fragmentsReverses the cisplatin resistance in A2780cis cellsA2780cis cells[101]
Deoxycholic acid conjugatedHP fragments (HFD)HP–drug conjugateInhibiting VEGF165SCC7 cells[102]
LMWH-SuraminHP–drug conjugateInhibiting VEGF165SCC7-bearing mouse model[103]
HP-suramin/PEGylated protamineHP–drug conjugateAntiangiogenic propertiesSCC7-bearing mouse model[104]
HP-functionalized Pluronic nanoparticlesPolymeric nanoparticlesAntiangiogenic properties and drug combinationGastric cancers[105]
Heparin/polyethyleneglycol (PEG) hydrogelNanogelsAntiangiogenic properties and drug combinationBreast cancer[106]
LMWH-poloxamerNanogelsEnhancing the efficacies, minimizing the side effects ofdalteparin, and exhibiting a good thermosensitivityXenograft S180 sarcoma tumor[107]
HP-containing cryogel microcarriersPolyelectrolyte complex nanoparticlesReversible strong electrostatic interactionMetastatic breast cancer[108]
HP-Folate-Tat-TaxolPolyelectrolyte complex nanoparticlesNegatively charged nanoparticles may cause lower toxic effectBreastcancer cells[109]
LMWH–quercetin conjugateHP–drug conjugateAntiangiogenic propertiesMCF-7 tumor cells[110]
HP-PoloxamerHP-coated inorganic nanoparticlesAntiangiogenic properties and drug combinationHeLa cells[111]
Heparosan-cystamine-vitamin E succinateNanogelsIncrease tumor selectivity and improve the therapeutic effectMGC80-3 tumor cells[112]
LMWH-TOSPolyelectrolyte complex nanoparticlesAntiangiogenic properties and drug combination4T1 solid tumor model[113]
HP–folate–retinoic acid bioconjugatesPolyelectrolyte complex nanoparticlesDrug combinationHeLa cells[114]
HP-reduced graphene oxide nanocompositesPolyelectrolyte complex nanoparticlesCombinational chemotherapy and photothermal therapyMCF-7 and A549cells[115]
PEGylated HP-based nanomedicinesPolyelectrolyte complex nanoparticlesPhotodynamic therapy4T1 cells[116]
Table
Table 6. Application of HA in antitumour therapy.
Table 6. Application of HA in antitumour therapy.
Compound HA Combination TypesAnticancer MechanismsTypes of CancerRef.
Carbon nanotubes-Chitosan (CHI)-HA-DOXPolymeric nanoparticlesCD44-targeted, hydrophilicHeLa cells[120]
HA-DOX-afatinib-CaPPolymeric nanoparticlesCD44-targeted, high-densitycarboxyl groupsA549 lung cancer cells[121]
HA-Curcumin (Cur)NanogelsCD44-targetedA549 lung cancer cells[122]
HA-SinulariolidePolymeric nanoparticlesCD44-targetedA549 lung cancer cells[123]
HA-Cur-prodrug-CaPPolymeric nanoparticlesCD44-targetedMB-MDA-231 mouse model[124]
HA-cystamin-pyrenyl-Ir(III)Polymeric nanoparticlesCD44-targeted, hydrophilicA549 tumor-bearing mice[125]
HA-DOX-cisplatinNanogelsCD44-targetedA2780 cell lines[126]
HA-keratin-DOXNanogelsCD44-targeted, negative charge and good hydrophilicity4T1 and B16 cells[127]
HA-PemetrexedHA–drug conjugateCD44-targeted, as a prognostic marker in malignant pleural mesotheliomaMalignant pleuralmesothelioma model[128]
HA-fluvastatin-encapsulating liposomesPolymeric nanoparticlesCD44-targeted, hydrophilic barrierBreast cancer stem cellxenografted mouse model[129]
HA-coated silica/hydroxyapatite- DOXHA-coated inorganic nanoparticlesCD44-targeted4T1 tumor-bearing mice[130]
HA-sclareol/poly-lactic-co-glycolic acidHA-coated inorganic nanoparticlesCD44-targeted, hydrophilicMCF-7 and MDA-MB468 cell lines[131]
HA-coated camptothecinHA-coated inorganic nanoparticlesCD44-targetedMDA-MB-231 cells[132]
HA and poly-(N-ε-carbobenzyloxy-L-lysine)Polymeric nanoparticlesCD44-targetedHepG2 tumor-bearing mice[133]
Ursolic acid-loadedin a poly-L-lysine coat and HAHA-coated organic nanoparticlesCD44-targetedSCC-7 xenograft tumor model[134]
folic acid- and dopamine-decorated HAHA-coated organic nanoparticlesCD44-targetedB16 melanoma model[135]
HA-Cu2−XSHA-coated organic nanoparticlesCD44-targeted, biocompatibilityCT26.WT cells-bearing mice[136]
HA Conjugated ZincProtoporphyrinHA conjugated cincprotoporphyrinCD44-targetedC26 colon cancer cells[137]
Irinotecan-loaded self-agglomerating HAPolymeric nanoparticlesCD44-targetedH23 non-small-cell lung cancer cells[138]
HA-SuperparamagneticIron OxidePolyelectrolyte complex nanoparticlesCD44-targetedU87MG cells[139]
Table
Table 7. Types of CS.
Table 7. Types of CS.
CS TypesMajor Disaccharide UnitOther Disaccharide Unit
CS-AGlcA-GalNAc4SGlcA-GalNAc/GlcA2S-GalNAc
CS-B(DS)IdoA-GalNAc4SIdoA2S-GalNAc4S/GlcA3S-GalNAc
CS-CGlcA-GalNAc6SIdoA-GalNAc4S6S/GlcA3S-GalNAc4S
CS-DGlcA2S-GalNAc6SIdoA2S-GalNAc4S6S/GlcA3S-GalNAc4S6S
CS-EGlcA-GalNAc4S6SIdoA2S-GalNAc/GlcA3S-GalNAc6S
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

**, H.; Li, M.; Tian, F.; Yu, F.; Zhao, W. An Overview of Antitumour Activity of Polysaccharides. Molecules 2022, 27, 8083. https://doi.org/10.3390/molecules27228083

AMA Style

** H, Li M, Tian F, Yu F, Zhao W. An Overview of Antitumour Activity of Polysaccharides. Molecules. 2022; 27(22):8083. https://doi.org/10.3390/molecules27228083

Chicago/Turabian Style

**, Hongzhen, Maohua Li, Feng Tian, Fan Yu, and Wei Zhao. 2022. "An Overview of Antitumour Activity of Polysaccharides" Molecules 27, no. 22: 8083. https://doi.org/10.3390/molecules27228083

Article Metrics

Back to TopTop