Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy

Abstract

Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to investigate the combined antitumor effect of paclitaxel with small interfering RNA modified by cationic liposome formed from modified octadecyl quaternized carboxymethyl chitosan. The cationic liposome was composed of 3β-[N-(N', N'-dimethylaminoethane)-carbamoyl]-cholesterol, dioleoylphosphatidylethanolamine, and octadecyl quaternized carboxymethyl chitosan. The cationic liposome properties were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and zeta potential measurements, transmission electron microscopy, atomic force microscopy, and gel retardation assay. The cationic liposome exhibited good properties, such as a small particle size, a narrow particle size distribution, a good spherical shape, a smooth surface, and a good binding ability with small interfering RNA. Most importantly, when combined with paclitaxel and small interfering RNA, the composite cationic liposome induced a great enhancement in the antitumor activity, which showed a significantly higher in vitro cytotoxicity in Bcap-37 cells than liposomal paclitaxel or small interfering RNA alone. In conclusion, the results indicate that cationic liposome could be further developed as a codelivery system for chemotherapy drugs and therapeutic small interfering RNAs.

Preparation and antitumor effect evaluation of composite microparticles co-loaded with siRNA and paclitaxel by a supercritical process

“…Alamar Blue was purchased from the American Invitrogen Company. Bcap-37 cells (P-gp dependent 31 ) were purchased from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). Dichloromethane (DCM, 99.8% purity) was purchased from the Sinopharm Chemical Reagent Co., Ltd (Shanghai, China).…”

Tumor-targeted nano-delivery system of therapeutic RNA

“…191 Octadecyl quaternized carboxymethyl chitosan exhibits high antitumor activity during the delivery of paclitaxel and small interfering RNA. 192 The second method is the introduction of lipophilic groups through acidogenic or atherogenic reactions. For example, gels synthesized using N -(2-hydroxy) propy1-3-trimethyl ammonium chitosan chlorides can effectively increase the concentration of siRNA in cells (Fig.…”

Chitosan-based advanced materials for docetaxel and paclitaxel delivery: Recent advances and future directions in cancer theranostics

“…By improving the targeted delivery of DTX and IGF-1R siRNA, high cellular uptake of DTX significantly diminishes the viability and proliferation of breast cancer cells and a decrease in cell growth and survival is observed due to inhibition of IGF-1R. Taking everything into account, it seems that CS modification of NPs has two major advantages: A) improving the biocompatibility of NPs, and B) providing a platform for attachment of drugs and genes [203][204][205].…”