Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer.
Despite progress, combination therapy of different functional drugs to increase the efficiency of anticancer treatment still remains challenges. An amphiphilic methoxy poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l-lysine) triblock copolymer decorated with deoxycholate (mPEsG-b-PLG-b-PLL/DOCA) was synthesized and developed as a nanovehicle for the co-delivery of anticancer drugs: doxorubicin (DOX) and paclitaxel (PTX). The amphiphilic copolymer spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and the blank nanoparticles possessed excellent stability. Three different domains of the copolymer performed distinct functions: PEG outer corona provided prolonged circulation, middle biodegradable and hydrophilic PLG shell was designed for DOX loading through electrostatic interactions, and hydrophobic deoxycholate modified PLL served as the container for PTX. In vitro cytotoxicity assays against A549 human lung adenocarcinoma cell line demonstrated that the DOX + PTX co-delivered nanoparticles (Co-NPs) exhibited synergistic effect in inducing cancer cell apoptosis. Ex vivo DOX fluorescence imaging revealed that Co-NPs had highly efficient targeting and accumulation at the implanted site of A549 xenograft tumor in vivo. Co-NPs exhibited significantly higher antitumor efficiency in reducing tumor size compared to free drug combination or single drug-loaded nanoparticles, while no obvious side effects were observed during the treatment, indicating this co-delivery system with different functional antitumor drugs provides the clinical potential in cancer therapy.
['Lv|Shixian|S|', 'Tang|Zhaohui|Z|', 'Li|Mingqiang|M|', 'Lin|Jian|J|', 'Song|Wantong|W|', 'Liu|Huaiyu|H|', 'Huang|Yubin|Y|', 'Zhang|Yuanyuan|Y|', 'Chen|Xuesi|X|']
D000818:Animals D000971:Antineoplastic Combined Chemotherapy Protocols D002289:Carcinoma, Non-Small-Cell Lung D003692:Delayed-Action Preparations D004058:Diffusion D004317:Doxorubicin D008175:Lung Neoplasms D008297:Male D008807:Mice, Inbred BALB C D008819:Mice, Nude D053769:Nanocapsules D053761:Nanocomposites D017239:Paclitaxel D010455:Peptides D014677:Pharmaceutical Vehicles D011092:Polyethylene Glycols D016896:Treatment Outcome
Nanoparticle Chemotherapy Controlled drug release Drug co-delivery Polypeptide