Immunoactive polysaccharide functionalized gold nanocomposites promote dendritic cell stimulation and antitumor effects
Abstract
Aim: To investigate the immune responses and antitumor efficacy of immunoactive polysaccharide functionalized gold nanocomposites (APS-AuNP). Materials & methods: Immunoregulation of APS-AuNP on dendritic cells/T cells in vitro was evaluated by flow cytometry and their inhibitions against primary/metastatic tumors were determined on 4T1-bearing mice model. Results & conclusion: APS-AuNP exhibited remarkable capability to induce dendritic cells maturation through phenotypic markers with functional changes, which further promoted T-cell proliferation and enhanced cytotoxicity against 4T1 tumor cells. The inhibitory rate of APS-AuNP against 4T1 primary tumor growth and pulmonary metastasis in mice was higher than paclitaxel-treated group. In addition, APS-AuNP exhibited strong capability to increase the population of CD4+/CD8+ T lymphocytes as well as effector memory cells rather than central memory cells.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Biomedical applications of gold nanoparticles. Curr. Top. Med. Chem. 15(16), 1605–1613 (2015).
- 2. . Gold nanoparticles: an era in bionanotechnology. Expert. Opin. Drug Deliv. 10(3), 397–409 (2013).
- 3. . Gold laced bio-macromolecules for theranostic application. Int. J. Biol. Macromol. 110, 39–53 (2018).
- 4. . Hyaluronan-inorganic nanohybrid materials for biomedical applications. Biomacromolecules 18(6), 1677–1696 (2017).
- 5. Portable amperometric immunosensor for histamine detection using Prussian blue-chitosan-gold nanoparticle nanocomposite films. Biosens. Bioelectron. 98, 305–309 (2017).
- 6. Development of noncytotoxic chitosan-gold nanocomposites as efficient antibacterial materials. ACS Appl. Mater. Interfaces 7(2), 1087–1099 (2015). • Example of conjugate of AuNP and low-immunogenic polysaccharide.
- 7. . Dose matters: direct killing or immunoregulatory effects of natural polysaccharides in cancer treatment. Carbohydr. Polym. 195, 243–256 (2018).
- 8. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother. Res. 28(9), 1275–1283 (2014).
- 9. A review of recent research progress on the Astragalus genus. Molecules 19(11), 18850–18880 (2014).
- 10. Advances on bioactive polysaccharides from medicinal plants. Crit. Rev. Food Sci. Nutr. 56, 60–84 (2016).
- 11. . Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int. J. Biol. Macromol. 64(2), 257–266 (2014).
- 12. . Astragalus polysaccharide alleviates LPS-induced inflammation injury by regulating miR-127 in H9c2 cardiomyoblasts. Int. J. Immunopathol. Pharmacol. 32, 1–11 (2018).
- 13. Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor beta and the frequency of regulatory T cells. FEMS Immunol. Med. Microbiol. 63(2), 228–235 (2011).
- 14. Enhancement of the innate immune response of bladder epithelial cells by Astragalus polysaccharides through upregulation of TLR4 expression. Biochem. Biophys. Res. Commun. 397(2), 232–238 (2010).
- 15. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci. Rep. 7, 44822–44835 (2017). •• A good paper for introducing the mechanism of APS for their immunoregulation.
- 16. TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells. J. Ethnopharmacol. 179(8), 243–252 (2016).
- 17. Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells. Int. J. Biol. Macromol. 93(Pt A), 940–951 (2016).
- 18. Comparative studies on the immunoregulatory effects of three polysaccharides using high content imaging system. Int. J. Biol. Macromol. 86(1), 28–42 (2016).
- 19. Immunobiology of dendritic cells. Annu. Rev. Immunoly. 18(1), 767–811 (2000).
- 20. Trial watch: dendritic cell-based anticancer immunotherapy. Oncoimmunology 6(7), 1328341 (2017).
- 21. . Dendritic cell-based immunotherapy: state of the art and beyond. Clin. Cancer Res. 22(8), 1897–1906 (2016). • Good review for introducing dendritic cell-based immunotherapy.
- 22. Dendritic cells as pharmacological tools for cancer immunotherapy. Pharmacol. Rev. 67(4), 731–753 (2015).
- 23. . Innovative strategies for co-delivering antigens and CpG oligonucleotides. Adv. Drug. Deliv. Rev. 61(3), 205–217 (2009).
- 24. Trial watch: immunostimulation with toll-like receptor agonists in cancer therapy. Oncoimmunology 5(3), 1088631 (2016). •• Good review for introducing the role of TLR agonists in cancer therapy.
- 25. Recent advances in the role of toll-like receptors and TLR agonists in immunotherapy for human glioma. Protein Cell 5(12), 899–911 (2014).
- 26. One pot light assisted green synthesis, storage and antimicrobial activity of dextran stabilized silver nanoparticles. J. Nanobiotechnol. 12(1), 53–59 (2014). •• A good article for introducing the synthesis procedure of polysaccharide-based nanocomposite.
- 27. Antibacterial activity of Ag-Au alloy NPs and chemical sensor property of Au NPs synthesized by dextran. Carbohydr. Polym. 107(8), 151–157 (2014).
- 28. Structural characterization and antioxidant activity in vitro of polysaccharides from Angelica and Astragalus. Carbohydr. Polym. 137, 154–164 (2016).
- 29. . Structural characterization of low molecular weight polysaccharide from Astragalus membranaceus and its immunologic enhancement in recombinant protein vaccine against systemic candidiasis. Carbohydr. Polym. 145, 48–55 (2016).
- 30. . A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 11(11), 55–75 (1951).
- 31. . Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3(2), 133–146 (2003).
- 32. . Mouse 4T1 breast tumor model. Curr. Protoc. Immunol. Chapter 20 Unit 20 22 (2001).
- 33. . Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22(1), 745–763 (2004).
- 34. . Hepatic metabolism of colloidal gold-low-density lipoprotein complexes in the rat: evidence for bulk excretion of lysosomal contents into bile. Hepatology 9(3), 380–392 (1989).
- 35. Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner. Cancer Res. 74(19), 5421–5434 (2014). • Interesting paper reporting the pathway for PTX-induced breast tumor metastasis.
- 36. . Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis. Proc. Natl Acad. Sci. USA 114(34), 7159–7168 (2017). • A good paper for introducing the possible mechanism of chemotherapy-exacerbated breast cancer metastasis.
- 37. . Current development in the formulations of non-injection administration of paclitaxel. Int. J. Pharm. 542(1-2), 242–252 (2018).
- 38. . Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J. Oncol. Pharm. Pract. 21(6), 451–467 (2015).
- 39. Radiation followed by OX40 stimulation drives local and abscopal antitumor effects in an anti-PD1-resistant lung tumor model. Clin. Cancer Res. 24(22), 5735–5743 (2018).
- 40. Radiotherapy and CD40 activation separately augment immunity to checkpoint blockade in cancer. Cancer Res. 78(15), 4282–4291 (2018).
- 41. Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc. Natl Acad. Sci. USA 113(46), 7240–7249 (2016).