Chemo-immunotherapy by dual-enzyme responsive peptide self-assembling abolish melanoma  

作　　者：Yuhan Wang Limin Xie Xinxin Li Ling Wang Zhimou Yang 

机构地区：[1]Tianjin Key Laboratory of Inflammation Biology,Department of Pharmacology,School of Basic Medicine,Tianjin Medical University,Tianjin,300070,PR China [2]Key Laboratory of Bioactive Materials,Ministry of Education,State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Collaborative Innovation Center of Chemical Science and Engineering,National Institute of Functional Materials,Nankai University,Tianjin,300071,PR China [3]State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy,Nankai University,Tianjin 300071,PR China

出　　处：《Bioactive Materials》2024年第1期549-562,共14页生物活性材料（英文）

基　　金：supported by the National Key Research and Development Program of China(2022YFB3804600);the National Natural Science Foundation of China(32171325,32301122 and 82261160656).

摘　　要：Herein,we designed Comp.1 to simultaneously respond to two enzymes:alkaline phosphatase and matrix metalloproteinase 2,which is commonly found in highly malignant cancer cell lines containing B16-F10 murine melanoma cells and CT26 murine colon carcinoma cells.We used the regional differences in the expression levels of dual-markers to accurately release immune molecule IND into tumor microenvironment for the activation of anti-tumor related immune effects,while in-situ self-assembly occurs.The dual-enzyme response process can further regulate the peptide precursors’self-assembly in the form of short rod-shaped nanofibers,enabling the delivery of the loaded chemotherapeutic drug HCPT into the cancer cells and further allowing the peptide assemblies to escape from lysosomes and return to cytoplasm in the form of tiny nanoparticles to induce apoptosis of cancer cells.This process does not occur in the single-positive breast cancer cell line MCF-7 or the normal hepatocytes cell line LO2,indicating the selectivity of the cancer cells exhibited using our strategy.In vivo studies revealed that Comp.1 can effectively cooperate with chemotherapy to enhance the immunotherapy effect and induce immune responses associated with elevated pro-inflammatory cytokines in vivo to inhibit malignant tumors growth.Our dual-enzyme responsive chemo-immunotherapy strategy feasible in anti-tumor treatment,provides a new avenue for regulating peptide self-assembly to adapt to diverse tumor properties and may eventually be used for the development of novel multifunctional anti-tumor nanomedicines.

关 键 词：Self-assembly Dual-enzyme responsive CHEMO-IMMUNOTHERAPY Procedural delivery Anti-tumor 

分 类 号：R730.51[医药卫生—肿瘤]