title: Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer.
abstract: 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.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Song
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun 130012, PR China.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: yzhang@wakehealth.edu.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: xschen@ciac.ac.cn.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000138:chemical synthesis*; D011092:Polyethylene Glycols / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D010455:Peptides; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel
keywords: Chemotherapy; Controlled drug release; Drug co-delivery; Nanoparticle; Polypeptide