基于脂质体/金纳米棒复合材料的光控药物释放体系及其胃癌治疗研究

Liposome/gold nanorod complex drug carriers are highly biocompatable, easily synthesized, light responsive and have multiple imaging modalities. However, studies on their drug release and imaging in vivo are limited due to low photothermal conversion efficiency and low imaging resolution (due to low loading of gold). In this project, we are going to first synthesize amphiphilic gold nanorods, followed by loading the gold nanorods into lipid bilayers using highly efficient reversed phase evaporation method. In this way, we can get highly coupled gold nanorods confined in lipid bilayers. Further, we load anticancer drug doxrubicin by remote loading. Hence, we can synthesize and choose the liposome/gold nanorod complex drug carriers with strong photoacoustic signal, high photothermal conversion coefficient, high drug release efficiency, good stability and low toxicity. After that, we will first get high inhibition of gastric cancer cells by complex drug carrier under illumination or hyperthemia, and then realize the high resolution photoacoustic imaging of gastric cancer tissue using the same drug carrier, and finally achieve high inhibition against gastric cancer tissue under illumination with the drug carrier. This project will offer a novel and highly efficient drug carrier to gastric cancer therapy.

脂质体/金纳米粒子复合药物载体具有生物相容性好、合成方便、光响应和成像模态丰富等优点。但是由于其光热转换效率较低或成像分辨率较低（由于金的载入量低）的问题，人们对其在体的药物控制释放和肿瘤的成像研究并不多。本项目拟先通过“grafting to”和“grafting from”法合成两亲性金纳米棒，再应用反向蒸发法高效地在脂质体双分子层膜内载入金纳米棒，实现金纳米棒在脂质体双分子层中的高度耦合，以提升单位质量金纳米棒的光声性质和光热转换效率。随后载入抗癌药物阿霉素，从而制备并筛选出光声信号强、光热转换系数高、药物释放效率高、稳定性好、毒性低的复合药物载体。在此基础上，首先在细胞层面上达到在光照或高温刺激后其对胃癌细胞的高效抑制作用，随后实现对胃癌组织的高分辨光声成像，最后完成光照后复合药物载体对胃癌组织的高效抑制作用。本项目为胃癌的治疗提供一种新型的高效的药物载体。

脂质体具有生物相容性好、合成方便、光响应和成像模态丰富等优点。本项目构建了针对肿瘤成像和治疗的多种脂质体纳米成像探针和纳米药物。构建了光响应和温度响应型诊疗性脂质体IR780-TSL，具有优异的光响应性能和温度响应性能。构建了基因治疗/化疗联合应用的脂质体纳米载体CL-DOX和AL-PDAD-MDR，能够有效抑制耐药性肿瘤细胞的生长。构建了化疗/化疗联合应用的脂质体纳米载体pHSL/TQR/DOX，能够完全逆转肿瘤耐药性并有效抑制耐药性肿瘤细胞的生长。构建了激活型脂质体荧光纳米探针TPE-LP，具有优异的肿瘤细胞成像能力，对肿瘤组织也具有较好的成像性能，信号背景比达3.8。构建了开关型脂质体荧光纳米探针TPE/BHQ-lipo，具有优异的肿瘤细胞成像能力，对肿瘤组织具有更好的成像性能，肿瘤信号背景比达4.8。本项目为肿瘤的成像和治疗提供了多种新型的脂质体荧光探针和纳米药物。在该项目支持下，我们以第一作者及通讯作者发表国际SCI 学术论文3篇，包括Chemical Society Reviews （IF 40）、Colloids and Surface B: Biointerfaces（IF 3.997），参与发表国际SCI学术论文2篇，包括ACS Appl Mater Interfaces ( IF7.1)、Peer J (IF 2.469)。