双响应型多功能纳米药物缓释体系的设计构建及其在生物方面的应用

In recent years, the nanomedicine system which is applied to the therapy of tumor has attracted much attention gradually. Our group is dedicating to study the multi-functional and di-sensitive (pH and temperature) nanocarrier Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO, which is related with magnetic induction heat, biological imaging and the controlled drug release. Through using 5-fluorouracil (5-FU) as a model drug, with Fe3O4 nanoparticles for magnetic induction heat chemotherapy particles, combined with temperature sensitive polymer poly (n-isopropyl acrylamide) (PNIPAM) in a reversible phase transition at the lowest critical temperature advantages， temperature sensitivity of drug controlled release, magnetic target drug delivery and magnetic heat treatment on tumor cell will be achieved. According to the microenvironment of tumor cells, which is acid and the heat resistance is significantly weaker than normal cells, we build the magnetic nanocarrier Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO, in which the controlled drug release is responsive to pH and temperature. ZnO quantum dot is used as the switch, which is responsive to pH. In addition,Through the experiments data for evaluating the controllability of drug release in vitro, the molecular mechanism of inducing tumor cell apoptosis is in preliminary research and discussion.

近年来，针对肿瘤细胞治疗的纳米药物体系逐渐引起了重视。本项目设计研究具有磁热功能、生物成像及药物控释等多功能为一体的双响应型（pH和温度）纳米药物传输体系Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO。通过以5-氟尿嘧啶（5-Fu）为药物模型，以Fe3O4 纳米粒子为体系中磁热响应粒子，结合温敏型聚合物聚N-异丙基丙烯酰胺（PNIPAM）在最低临界温度处的可逆相变的优势带来的温度响应性来实现对药物的温敏性控释，以及对肿瘤细胞的磁热治疗及磁靶向传送药物的功能；同时，根据肿瘤细胞外的微环境偏弱酸性且其耐热性明显弱于正常细胞的特点，以ZnO量子点为pH响应开关，构建由温度和pH共同控制药物释放的磁性纳米药物载体Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO。根据体内，体外实验评价该药物载体的药物释放，进一步研究该药物传输体系对肿瘤细胞凋亡的影响。

本项目设计研究具有磁热功能、生物成像及药物控释等多功能为一体的双响应型（pH和温度）纳米药物传输体系Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO。通过以5-氟尿嘧啶（5-Fu）为药物模型，以Fe3O4 纳米粒子为体系中磁热响应粒子，结合温敏型聚合物聚N-异丙基丙烯酰胺（PNIPAM）在最低临界温度处的可逆相变的优势带来的温度响应性来实现对药物的温敏性控释，以及对肿瘤细胞的磁热治疗及磁靶向传送药物的功能；同时，根据肿瘤细胞外的微环境偏弱酸性且其耐热性明显弱于正常细胞的特点，以ZnO量子点为pH响应开关，构建由温度和pH共同控制药物释放的磁性纳米药物载体Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO。根据体内，体外实验评价该药物载体的药物释放，进一步研究了该药物传输体系对肿瘤细胞凋亡的影响。我们还设计构建了另外三个多功能肿瘤治疗体系Fe3O4/PNIPAM/5-Fu@mSiO2-CHI/R6G、MnO2/Fe3O4/5-Fu@CHI/R6G、CaO2/MnO2@PDA-MB。