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

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.