Antibody-activated trans-endothelial delivery of mesoporous organosilica nanomedicine augments tumor extravasation and anti-cancer immunotherapy

作     者：Tinglei Huang Shuang Li Jianchen Fang Fuli Li Shuiping Tu 

作者机构：Department of OncologyState Key Laboratory of Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China Department of StomatologyRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China Department of PathologyRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2021年第6卷第7期

页      面：2158-2172页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was financially supported by the National Natural Science Foundation of China(NSFC 81472727,NSFC 81773259 and NSFC 91029718) Science and Technology Commission of Shanghai Municipality(15JC1403100) National laboratory of Oncogene and Cancer-related Genes foundation(90-15-05) 

主　　题：Active transcytosis Extravasation Drug delivery Cancer immunotherapy Stimulus-responsive nanomedicine 

摘      要：Tumor vasculature constitutes a formidable hurdle for the efficient delivery of cancer nanomedicine into *** leverage of passive pathway through inter-endothelial gaps in tumor blood vessels might account for limited extravasation of nanomedicine into tumor microenvironment(TME).Herein,Annexin A1 antibody-installed mesoporous organosilica nanoplatforms carrying immunotherapeutics of anti-PD-L1 antibody(aPD-L1)and Indoximod are developed to target at caveolar Annexin-A1 protein of luminal endothelial cells and to trigger the active trans-endothelial transcytosis of nanomedicine mediated by *** strategy enables rapid nanomedicine extravasation across tumor endothelium and relatively extensive accumulation in tumor ***-L1 and Indoximod release from aPD/IND@MON-aANN in a reduction-responsive manner and synergistically facilitate the intratumoral infiltration of cytotoxic T lymphocytes and reverse the immunosuppressive TME,thus demonstrating substantial anti-tumor efficacy in subcutaneous 4T1 breast tumors and remarkable anti-metastatic capacity to extend the survival of 4T1 tumor metastasis ***,aPD/IND@MON-aANN nanomedicine also exhibits distinct superiority over the combination therapy of free drugs to potently attenuate the progression of urethane-induced orthotopic lung ***,aPD/IND@MON-aANN nanoplatforms with boosted delivery efficiency via antibody-activated trans-endothelial pathway and enhanced immunotherapeutic efficacy provides perspectives for the development of cancer nanomedicines.