Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy  

作　　者：Chenglin Liang Ge Zhang Linlin Guo Xinyi Ding Heng Yang Hongling Zhang Zhenzhong Zhang Lin Hou 

机构地区：[1]School of Pharmaceutical Sciences,Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Zhengzhou University,Zhengzhou 450001,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第1期103-118,共16页亚洲药物制剂科学（英文）

基　　金：was supported by National Natural Science Foundation of China(81972893,82172719);Natural Science Foundation of Henan(212300410071);Training program for young key teachers in Henan Province(2020GGJS019).

摘　　要：Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

关 键 词：Cells senescence Tumor stroma Structure transformable Programmed delivery Anti-tumor immunotherapy 

分 类 号：R943[医药卫生—药剂学]