Combining chemotherapy and photodynamic therapy (PDT) with a nanoscale drug delivery system (NDDS) has been widely developed to improve the therapeutic efficacy and biological safety of current treatments. However, the excess glutathione (GSH) in tumor cells impedes the ROS generation from photosensitizers, leading to reduction of PDT efficacy. Moreover, most NDDS also have been restricted due to the complexity of the multi-component, batch to batch differences, carrier-related toxicity and poor drug loading issues. To overcome these problems, a novel carrier-free nanodrug (GA-Ce6-FA NPs) was developed to achieve chemotherapy combined PDT synergistic treatment by a simple and green self-assembly approach, and the NPs was made up of gambogic acid (GA), chlorin e6 (Ce6) and folic acid (FA), in which GA was not only used as a chemotherapy drug but also designed to deplete GSH in tumor for enhancing PDT efficacy. The GA-Ce6-FA NPs exhibited a diameter of ∼135 nm, which favored the NPs accumulation in tumor by a potential EPR effect. Meanwhile, the GA-Ce6-FA NPs had a pH-triggered drug release profile under a weak acidic condition, which could fast release drugs at the tumor region. It significantly enhanced the intracellular Ce6 uptake due to FA active targeting. Moreover, GA-Ce6-FA NPs could induce efficient apoptosis of MCF-7 cells, and offer a significant anti-tumor function by chemotherapy-PDT, which indicated depleting GSH by chemotherapeutics was an effective way to improve the efficacy of PDT. Thus, by the carrier-free NPs, a strategy of using multi-functional anticancer drugs as endogenous synergistic agents to PDT is useful to enhance anti-tumor efficacy.

将化学疗法和光动力疗法（PDT）与纳米级药物递送系统（NDDS）相结合已得到广泛开发，以提高当前疗法的治疗功效和生物安全性。但是，肿瘤细胞中过量的谷胱甘肽（GSH）会阻止光敏剂产生ROS，从而导致PDT功效降低。此外，由于多组分的复杂性，批次之间的差异，与载体有关的毒性和不良的药物装载问题，大多数NDDS也受到限制。为了克服这些问题，开发了一种新型的无载体纳米药物（GA-Ce6-FA NPs），可通过简单且绿色的自组装方法实现化学疗法与PDT的协同治疗，并且NPs是由藤黄酸（GA）组成的，二氢卟酚e6（Ce6）和叶酸（FA），其中GA不仅被用作化学治疗药物，而且还被设计用于消灭肿瘤中的GSH以增强PDT的功效。GA-Ce6-FA NP的直径约为135 nm，通过潜在的EPR效应促进了NP在肿瘤中的蓄积。同时，GA-Ce6-FA NPs在弱酸性条件下具有pH触发的药物释放曲线，可以在肿瘤区域快速释放药物。由于FA主动靶向，它显着增强了细胞内Ce6的摄取。此外，GA-Ce6-FA NPs可诱导MCF-7细胞有效凋亡，并通过化学疗法-PDT提供显着的抗肿瘤功能，这表明化学疗法消耗GSH是提高PDT疗效的有效途径。因此，通过无载体的NP，