Yaping Li
Chinese Academy of Sciences, China
Title: Metastatic cancer therapy using ph-responsive nanoparticles for sirna and anticancer drug co-delivery
Biography
Biography: Yaping Li
Abstract
The combination of chemotherapy and RNA interference is a promising approach for efficient cancer therapy. However, the success of such a strategy is hampered by the lack of suitable vectors to coordinate small interfering RNA (siRNA) and chemotherapeutic drug into one single platform. We herein report a novel triple-layered pH-responsive micelleplex loading siRNA and anticancer drugs for treatment of metastatic breast cancer. The micelles were self-assembled from acidic pH-sensitive amphiphilic copolymers. At pH 7.4, the therapeutics (e.g., paxlitaxel, alkynated cisplatin and doxorubicin) was encapsulated in the hydrophobic micelle core and siRNA was loaded on the positively charged micelle shell to form the micelleplexes. The PEG corona can prevent protein absorption during blood circulation, minimize non-specific interaction with the reticuloendothelial system, and prolong the systemic circulation of the micelleplexes. Upon cellular uptake, the micelles are dissociated in the early endosomes to release anticancer drug payload due to protonation of the micelle core. Using a 4T1 breast cancer model, we demonstrate that this novel micelleplex co-loaded with anti-cancer drugs and siRNA is able to simultaneously inhibit tumor growth and suppress distant metastasis of the cancer cells by blocking the signaling pathway regulating tumor metastasis. The results reported in this study suggest that siRNA and anticancer drug co-delivery using pH-responsive micelleplexes is a promising strategy for efficient treatment of metastatic cancer.