目前，多数肿瘤如乳腺癌通过单一手术治疗的方式无法根治，而化疗药物的毒副作用严重影响治疗效果。联合治疗协同抗肿瘤成为高效、低毒肿瘤治疗的发展方向。本项目通过将近红外探针Cypate与表阿霉素/NH4HCO3共负载，构建一种基于CO2气体介导的pH/近红外光双重响应多功能脂质体药物输送系统。Cypate具有近红外荧光成像与光热转换功能，既赋予脂质体肿瘤成像与热疗效应，也赋予其光热效应引发的CO2介导快速释药特性，实现光热化疗协同抗肿瘤；同时，利用具有肿瘤组织pH响应的磺胺衍生物（mPEG-PSD）与脂质体表面的静电吸附/解离，实现脂质体的长循环与促进肿瘤细胞摄取，达到其在肿瘤组织与细胞逐级递送的目的。本项目通过考察脂质体的近红外光响应性、pH响应性及CO2气体介导的快速释药对其细胞摄取、组织分布及体内外抑瘤效果的影响，揭示脂质体光热化疗协同抗肿瘤机制，为实现高效、低毒的肿瘤治疗提供依据。

Currently, it is difficult to achieve good therapeutic effect towards most tumor such as breast cancer using surgical treatment only. Besides, the therapeutic efficacy could be significantly affected by the side effects of chemotherapy drugs. Thus, the combination therapy for the treatment of cancer has become the better approach with high efficiency and low toxicity. In this project, we propose a novel liposome drug delivery system owning CO2 induced drug release and pH/near-infrared light double-responsive features through the encapsulation of near-infrared probe Cypate, epirubicin and CO2 initiator through NH4HCO3 gradient method. Cypate possess multiple functions such as fluorescence imaging and photothermal conversion induced by near-infrared light. Under near-infrared light irradiation, the photothermal agent could raise the temperature in order to kill tumor cells effectively. Then, the high temperature could simultaneously induce CO2 release from NH4HCO3 to promote the rapid release of anticancer drug in tumor site. Furthermore, the surface of liposome was shielded electrostatically with a pH-sensitive mPEG-PSD at pH 7.4, whereas mPEG-PSD was deshielded at tumor pH. It makes the carrier become long circulating in circulatory system but facilitate cellular uptake in tumor tissues. The photothermal chemotherapy could greatly improve the therapeutic effect towards cancer. In summary, we are devoted to investigate the cellular uptake, tissue distribution and antitumor effect of this multifunctional liposome with the influence of pH/NIR responsive and CO2 induced rapid release, reveal the combined anti-tumor mechanism between photothermal therapy and chemotherapy. We anticipate that this study could provide methodological and theoretical basis for high efficiency and low toxicity cancer therapy of liposome drug delivery system.