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

查看全文 作　　者：Lei [1,2]Jiang;Yang [1]Ding;Xialin [1]Xue;Sensen [2]Zhou;Cheng [2]Li;Xiaoke [2]Zhang;Xiqun [2]Jiang 高影响力作者 机构地区：[1]State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China;[2]MOE Key Laboratory of High Performance Polymer Materials and Technology, and Department of Polymer Science & Engineering,College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, China高影响力机构 出　　处：《Nano Research》索引2018年第11卷第11期,共12页高影响力期刊 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). 摘　　要：Developing multifunctional nanoparticles to support new therapy models is apromising and challenging task to address the current dilemma on antitumortreatment. Herein, we incorporated multifunctional dendritic nanoparticles intoa poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,Lqactide-co-glycolide)(PLGA-PEG-PLGA) triblock copolymers thermosensitive injectable hydrogelmatrix to construct a localized drug delivery system for combining chemotherapyand immunotherapy. The multifunctional dendritic nanoparticles were designedwith following expectations: i, Dendritic scaffolds provide a hydrophobic interiorto load the anticancer drug, doxorubicin (DOX), for chemotherapy; and ii,dendritic scaffolds are used to build arginine-rich molecules to provide theinducible nitric oxide synthase (iNOS) substrate, L-Arg, to M1 macrophages,which can produce the cytotoxic substance nitric oxide (NO) and subsequentlyinduce tumor cell destruction through immunotherapy. It is noteworthy that thedendritic nanoparticles-in-hydrogel delivery system is able to gel at physiologicaltemperature and serves as a warehouse for the sustained release of the drug.Ultimately, this system showed great efficacy in treating 4T1 cells-xenograftedBALB/C mice (86.62% tumor growth inhibition). Therefore, this localized drugdelivery system combining chemotherapy and immunotherapy provides a novelapproach for cancer therapy. 关 键 词：MULTIFUNCTIONAL DENDRITIC nanopartides peptide DENDRIMER cancer therapy combined chemotherapy and IMMUNOTHERAPY
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