Natural Synergy-Based Nanosystem Co-Delivering siRNA and Paclitaxel for Full-Stage Apoptosis Promotion in Melanoma

Abstract

Paclitaxel (PTX) kills tumors cells by stabilizing microtubules to induce apoptosis, but its efficacy is limited by resistance mediated by the anti-apoptotic protein Survivin. Targeting inhibition of Survivin with siRNA could synergistically enhance PTX-induced apoptosis; However, nucleic acid-based therapeutics, such as siRNA, exhibit high instability and susceptibility to degradation, making their efficacy highly dependent on specialized delivery systems. Thus, co-delivery systems for PTX and siRNA are critical to achieve synergistic antitumor activity. Natural products present several advantages, including wide availability, high biocompatibility, and multi-target synergistic effects, offering promising approaches to construct a co-delivery system. In this study, a co-delivery system integrating siRNA and PTX based on natural products was developed. Ginsenoside Rg3 (Rg3) not only serves as the structural backbone but also enhances tumor-targeting capability and inhibits tumor cell migration. The edible cationic polymer chitooligosaccharide (COS) efficiently encapsulates siRNA, ensuring safe and efficient delivery. This Co-delivery system based on natural synergy enables multi-level cooperation: Rg3 mediates targeted transport, PTX triggers apoptosis, and COS-assisted siRNA silences Survivin, thereby ensuring precise targeting and promoting complete tumor apoptosis, highlighting a promising strategy for the application of natural products in cancer therapy.