Rg3-PLGA@TMVs May Be the Candidates for Potential Inclusion in Cancer Therapy
Introduction
Natural products, including single components or extracts of herbal medicines, have the features of good efficacy and low toxicity when used in tumor treatment. They have unique advantages in treating diseases compared with chemotherapeutic drugs due to their multi-component and multi-target effects.Strikingly, ginsenoside Rg3-loaded PLGA nanoparticles (Rg3-PLGA) coated with the membrane of tumor cell-derived microvesicles (Rg3-PLGA@TMVs), which is a nanoformulation of the natural product ginsenoside Rg3, have a significant role in the treatment of breast cancer when combined with the chemotherapeutic drug doxorubicin (DOX).
Pharmacological roles of ginseng Rg3 in traditional Chinese medicine
Ginseng Rg3, a tetracyclic triterpenoid saponin, is one of the main active component of ginseng. Ginseng has been regarded as one of the most valuable medicinal plants in Chinese traditional medicine for thousands of years, which is known as "the king of all tonic”. This perennial herb possesses the multiple pharmaceutical functions such as tonifying the vital energy, restoring the pulse and stabilizing the loss of vitality, invigorating spleen and benefiting lung, generating saliva or body fluid to quench thirst, as well as tranquilizing the mind and promoting the intelligence.The construction of Rg3-PLGA@TMVs
Ginsenoside Rg3 is first encapsulated into PLGA nanoparticles using the nanoprecipitation method, followed by the extrusion-based coating of the TMV membrane onto Rg3-PLGA. This strategy combines the therapeutic properties of Rg3 with the precise delivery and sustained release capabilities of PLGA nanoparticles, further enhanced by the homologous targeting properties of TMVs.Anti-tumor effect and bio-safety of Rg3-PLGA@TMVs in 4T1 breast cancer
Rg3-PLGA@TMVs induce robust anti-tumor immunity, recover the body weight loss caused by DOX in 4T1 breast cancer and overtly improve the anti-tumor effect of DOX, showing good stability and drug loading capability. These anti-tumor effects are chiefly realized by reducing phagocytic activity and acid phosphatase (ACP) levels, promoting the maturation of bone marrow-derived dendritic cells in vitro, and elevating the population of cytotoxic T lymphocytes (CD3+CD8+) and helper T cells (CD3+CD4+) in vivo.
Importantly, this nanoformulation has minimal side effects and favorable biocompatibility, which can relieve the organ toxicity caused by DOX, especially the cardiac side effects. The administration of DOX and Rg3-PLGA@TMVs does not result in statistically significant changes in white blood cell (WBC) count and renal functional indicators, such as CREA and urea, nor in hepatic functional indicators, including AST and ALT.
Conclusion
Rg3-PLGA@TMVs achieve the co-delivery of antigens and adjuvants, which not only potentiate the anti-tumor effects, but also significantly alleviate the systemic toxicity caused by chemotherapeutic drugs, improving the overall health status of patients undergoing chemotherapy.Reference
[1] Liu XR, Zhang KF, Li X, et al. Research progress on antitumor nanoscale drug delivery system of ginsenoside Rg3 [J]. Chin Trad Herb Drugs. 2023,54(22):7577-7587. DOI: 10.7501/j.issn.0253-2670.2023.22.034
[2]Zhang S, Zheng B, Wei Y, et al. Bioinspired ginsenoside Rg3 PLGA nanoparticles coated with tumor-derived microvesicles to improve chemotherapy efficacy and alleviate toxicity [J]. Biomater Sci. Published online April 10, 2024. DOI:10.1039/d4bm00159a
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