Fabrication of Ginsenoside-Based Nanodrugs for Enhanced Antitumor Efficacy on Triple-Negative Breast Cancer

Abstract

There is an urgent need to identify chemotherapeutic agents with improved efficacy and safety against triple-negative breast cancer (TNBC). Ginsenosides can reportedly induce tumor cell death, invasion, and metastasis; however, poor water solubility, low oral absorption rate, and rapid blood clearance limit their clinical application. Utilizing the amphiphilic property of ginsenosides as building blocks of biomaterials, we fabricated a carrier-free nanodrug composed of ginsenosides Rg3 and Rb1 using a nano-reprecipitation method without any additional carriers. After characterizing and demonstrating their uniform morphology and pH-sensitive drug release properties, we observed that Rg3-Rb1 nanoparticles (NPs) exhibited stronger antitumor and anti-invasive effects on TNBCs in vitro than those mediated by free ginsenosides. Consequently, Rg3-Rb1 NPs afforded superior inhibition of tumor growth and reduction of pulmonary metastasis than the Rg3 and Rb1 mixture, with no obvious systematic toxicity in vivo. Collectively, our results provide a proof-of-concept that self-assembled engineered ginsenoside nanodrugs may be efficient and safe for TNBC therapy.

Unveiling the experimental proof of the anticancer potential of ginsenoside Rg3 (Review)

“…Various types of ginsenoside nanomedicines have shown potential in the treatment of different tumors, including triple-negative breast cancer ( 60 ). The in vivo delivery results of a multifunctional black phosphorus (BP) nanoreagent, BPs/G-Rg3@PLGA, demonstrated its notable therapeutic effect on lung metastases from breast cancer, along with significant biocompatibility with various organs/tissues ( 61 ).…”

“…Given that reaching the concentration of GS-Rg3 required to inhibit cancer cell growth in vivo is challenging, efforts should also be focused on investigating new methods to improve the solubility of GS-Rg3 without decreasing the efficacy of the drug, such as in the development of cofactors to aid in solubilization. The combination of GS-Rg3 with cholesterol transport liposomes as an alternative approach has shown greater therapeutic efficacy, reduced toxicity and the potential for overcoming drug resistance, exhibiting certain synergistic effects with anticancer drugs ( 60 ). Additionally, GS-Rg3 has displayed functions that are independent of its anticancer effects, such as enhancing biocompatibility and pharmacokinetics, which offer new directions for its optimal utilization.…”

The efficacy of natural products for the treatment of nasopharyngeal carcinoma

“…The stability of oridonin is poor and the half‐life is short in vivo (Chen, Luo, et al., 2019). Ginsenoside have poor intestinal permeability leading to low absorption rate (Zuo et al., 2022). Most chemotherapy or the combination of chemotherapy and radiation exacerbates the adverse reactions.…”

Anti-cancer effect and potential microRNAs targets of ginsenosides against breast cancer

“…Such as, ginsenoside F2 inhibits the proliferation of breast cancer stem cells (CSCs) by regulating p53 to induce apoptosis and stimulate autophagy ( Mai et al, 2012 ). Ginsenoside Rb1 can decrease tumor growth and tumor weight in vivo , and induce apoptosis of BC cells in vitro by binding to carbon nanotubes ( Lahiani et al, 2017 ; Zuo et al, 2022 ). Moreover, ginsenoside Rb3 increases the anti-proliferative activity of cisplatin at higher concentrations ( Aung et al, 2007 ).…”