Abstract
Due to the limitations of conventional chemotherapy including side effects,poor prognosis,and drug resistance,there is an urgent need for the development of a novel multi-functional combined therapy strategy.Dopamine-modified oxaliplatin prodrug(OXA-DA)was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects,and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparti-cle for loading siPD-L1 to construct multifunctional nanoplatform.The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline)(PEOz),which occurred charge reversal in the tumor microenvi-ronment,and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1(siPD-L1).The pH-responsive charge reversal,photothermal,biodegradation,lysosomal escape ability,PD-L1 protein degradation,toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments.The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a re-sult of the synergistic effect of chemo-photothermal therapy,and upregulated CD8+T cells produced interferon-γ(IFN-y)to further attack the tumor cells.In conclusion,the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.
基金项目
国家自然科学基金(32071342)
国家自然科学基金(32101065)
广东省自然科学基金(2023A1515012015)
广东省自然科学基金(2022A1515110271)
广东省自然科学基金(2020A1515011353)
NETL
NSTL
维普
万方数据