针对肿瘤光动力治疗（PDT）中纳米光敏剂在肿瘤部位的起效位置和剂量不可控促发免疫耐受的问题，本项目提出了一种光控脉冲释药的长循环脂质体，将大部分光敏剂递送至肿瘤细胞而非肿瘤血管、同时根据治疗需要“开启”和“关闭”释放行为。构建该脂质体的基本思路是：将胆固醇分子与光热探针cy7.5偶联，设计cholesterol-cy7.5修饰的Ce6脂质体。给予光照后，cy7.5的光热效应引发探针振动，带动偶联的胆固醇长轴转动，增加脂质体膜的通透性，引发内水相中Ce6的光控释放并以小分子形式跨越血管作用于肿瘤深部细胞；反之，关闭光照时，脂双层膜闭合，Ce6停止释放。本设计可精确控制光敏剂在肿瘤组织的释放动力学，特异性杀伤肿瘤细胞，调控肿瘤的免疫微环境，提高肿瘤治疗效果。发展出一种光敏剂起效位置和释放行为双重可控的脂质体，为光敏剂的智能递送以及PDT解除肿瘤免疫耐受、抑制肿瘤的复发和转移提供了新方法和技术。

Photodynamic therapy was hindered by the uncontrolled release location and dose of photosensitizers, which would induce the immune tolerance. Herein, we propose a light-tuned stealth liposome, which can deliver most photosensitizers to tumor cells instead of tumor blood vessels and precisely control the release kinetics to "on" and "off" release behavior according to therapeutic purpose. The long circulating liposomes are designed by coupling cholesterol with the photothermal probe cy7.5 and modifying Ce6 liposomes using cholesterol-cy7.5. After the laser irradiation, the light vibration is triggered by thermal effect of cy7.5, driving the rotation of the coupled cholesterol, increasing the permeability of the liposome membrane and causing the release of Ce6 which can deeply penetrate tumor stroma to tumor cells; conversely, when turning off the laser irradiation, lipid bilayer membrane reseal and the release of Ce6 stop. This nanosensitizer will precisely control the release kinetics in tumor, specifically kill tumor cells through a necrosis mechanism and modulate the immune microenvironment, thereby enhance the antitumor efficacy. Our technique may develop long circulating liposomes which can control the effective site and dose of photosensitizer and provide an important new tool for the intelligent delivery of photosensitizers, the tumor immune tolerance relieving and the inhibition of tumor recurrence and metastasis.