Entrapping multifunctional dendritic nanoparticles into a hydrogel for local therapeutic delivery and synergetic immunochemotherapy

作     者：Lei Jiang Yang Ding Xialin Xue Sensen Zhou Cheng Li Xiaoke Zhang Xiqun Jiang 

作者机构：State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 China MOE Key Laboratory of High Performance Polymer Materials and Technology and Department of Polymer Science & EngineeringCollege of Chemistry & Chemical Engineering Nanjing University Nanjing 210093 China 

出 版 物：《Nano Research》 (纳米研究（英文版）)

年 卷 期：2018年第11卷第11期

页      面：6062-6073页

核心收录：

学科分类：07[理学] 

基　　金：This work was supported by the National Natural Science Foundation of China (Nos. 81601594  51690153  21474045  and 21720102005) and the National Key R&D Program of China (No. 2017YFA0205400) 

主　　题：multifunctional dendritic nanoparticles peptide dendrimer cancer therapy combined chemotherapy and immunotherapy 

摘      要：Developing multifunctional nanoparticles to support new therapy models is a promising and challenging task to address the current dilemma on antitumor treatment. Herein, we incorporated multifunctional dendritic nanoparticles into a poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers thermosensitive injectable hydrogel matrix to construct a localized drug delivery system for combining chemotherapy and immunotherapy. The multifunctional dendritic nanoparticles were designed with following expectations: i, Dendritic scaffolds provide a hydrophobic interior to load the anticancer drug, doxorubicin (DOX), for chemotherapy; and ii, dendritic scaffolds are used to build arginine-rich molecules to provide the inducible nitric oxide synthase (iNOS) substrate, L-Arg, to M1 macrophages, which can produce the cytotoxic substance nitric oxide (NO) and subsequently induce tumor cell destruction through immunotherapy. It is noteworthy that the dendritic nanoparticles-in-hydrogel delivery system is able to gel at physiological temperature and serves as a warehouse for the sustained release of the drug. Ultimately, this system showed great efficacy in treating 4T1 cells-xenografted BALB/C mice (86.62% tumor growth inhibition). Therefore, this localized drug delivery system combining chemotherapy and immunotherapy provides a novel approach for cancer therapy.