Tumor acid microenvironment-activated self-targeting&splitting gold nanoassembly for tumor chemo-radiotherapy  

作　　者：Xiaomin Li Licheng Yu Chuangnian Zhang Xiaoyan Niu Mengjie Sun Zichao Yan Wei Wang Zhi Yuan 

机构地区：[1]Key Laboratory of Functional Polymer Materials of Ministry of Education,College of Chemistry,Nankai University,Tianjin,300071,China [2]Tianjin Key Laboratory of Biomaterial Research,Biomedical Barriers Research Center,Institute of Biomedical Engineering,Chinese Academy of Medical Science&Peking Union Medical College,Tianjin,300192,China [3]Collaborative Innovation Center of Chemical Science and Engineering,Nankai University,Tianjin,300071,China

出　　处：《Bioactive Materials》2022年第1期377-388,共12页生物活性材料（英文）

基　　金：This study is dedicated to 100th anniversary of Chemistry at Nankai University.This work was supported by the National Natural Science Foundation of China(Grant 52073147,51773096,51433004,32071342);Specific Program for High-Tech Leader&Team of Tianjin Government,Tianjin innovation and Promotion Plan Key Innovation Team of Immunoreactive Biomaterials.We appreciate Prof.Qiang Wu at Nankai University for help with the characterization of materials and Dr.Ding Yuxun for help with characterization of penetration.

摘　　要：Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy.Herein,a pH-responsive gold nanoassembly is designed to overcome these problems.Polyethylene glycol linked raltitrexed(RTX,target ligand and chemotherapy drug)and two tertiary amine molecules(1-(2-aminoethyl)pyrrolidine and N,N-dibutylethylenediamine)are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX).The Au-NNP(RTX)nanoassembly could remain at about 160 nm at the blood circulation(pH 7.4),while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH(pH 6.8).This pH-responsive disassembly behavior endows Au-NNP(RTX)better tumor tissue permeability through the better diffusion brought by the size reduction.Meanwhile,after disassembly,more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability.Most importantly,the results show that Au-NNP(RTX)possesses of high tumor accumulation and effective tumor penetration,thereby enhancing the tumor chemo-radiotherapy efficiency.

关 键 词：Gold nanoassembly Disassemble Penetration Self-target CHEMO-RADIOTHERAPY 

分 类 号：R73[医药卫生—肿瘤]