Light-activated arginine-rich peptide-modified nanoparticles for deep-penetrating chemo-photo-immunotherapy of solid tumor  

作　　者：Yonghua Gong Jinyang Zhang Yan Lu Dong Wan Jie Pan Guilei Ma 

机构地区：[1]Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy,The Tianjin Key Laboratory of Biomaterials,Institute of Biomedical Engineering,Peking Union Medical College&Chinese Academy of Medical Sciences,Tianjin 300192,China [2]School of Environmental and Chemical Engineering,Tiangong University,Tianjin 300387,China

出　　处：《Nano Research》2023年第7期9804-9814,共11页纳米研究（英文版）

基　　金：We acknowledge financial support from National Natural Science Foundation of China(Nos.82172089,22178270 and 22078246);the Fundamental Research Funds for the Central Universities(No.2019PT320028);CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-058).

摘　　要：Poor permeation of drugs and“immune-cold”tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment.Here,light-activated penetrable nanoparticles(PEGVAL&DOX&ICG@RNPs)for co-delivery of the chemotherapeutic drug doxorubicin(DOX),the photosensitizer agent indocyanine green(ICG),and the angiotensin II receptor blockers valsartan(VAL)were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor.Studies showed that under the first-wave of laser irradiation,the polyethylene glycol(PEG)hydrophilic layer as an“inert”surface could detach from the nanoparticles,release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway.When exposed to the second-wave of laser irradiation,the synergistic chemo-photo-immunotherapy can be achieved.As expected,in 4T1 tumorbearing mice,PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors,down-regulateα-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors,induce dendritic cells(DCs)maturation,and promote intratumoral infiltration of cytotoxic T lymphocytes.Moreover,combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo.This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of“immune-cold”solid tumor treatment.

关 键 词：light-activated nanoparticles TRANSCYTOSIS deep penetration chemo-photo-immunotherapy solid tumor 

分 类 号：R730.51[医药卫生—肿瘤]