基于脂质体的药物递送系统（DDSs）是减轻化疗副作用和大幅提高治疗效果的潜在工具。然而，要实现具备单一功能或单一机制的脂质体的生物安全、精确和高效癌症治疗存在挑战。为解决这一问题，我们设计了一种基于聚多巴胺（PDA）包被的脂质体的多功能和多机制纳米平台，用于化疗和激光诱导PDT / PTT的准确和高效联用癌症治疗。ICG和DOX被共同包含在聚乙二醇修饰脂质体中，进一步通过简便的两步法用PDA包被来构建PDA-脂质体纳米粒子（PDA@Lipo / DOX / ICG）。对正常HEK-293细胞的纳米载体安全性进行了调查，对人乳腺癌细胞MDA-MB-231的细胞摄取、细胞内ROS产生能力和纳米粒子的联合治疗效果进行了评估。基于MDA-MB-231皮下肿瘤模型，估计了体内分布、热成像、生物安全评估和联合治疗效果。与DOX · HCl和Lipo / DOX / ICG相比，PDA@Lipo / DOX / ICG对MDA-MB-231细胞的毒性更高。目标细胞内吞后，PDA@Lipo / DOX / ICG通过808 nm激光照射产生大量ROS进行PDT，联合治疗的细胞抑制率达到80.4％。在携带MDA-MB-231肿瘤的小鼠中进行尾静脉注射（DOX当量2.5 mg / kg）后，PDA@Lipo / DOX / ICG在注射后24 h显著堆积于肿瘤部位。在此时点（808 nm激光辐照1.0 W / cm²，2分钟）之后，PDA@Lipo / DOX / ICG有效抑制了MDA-MB-231细胞的增殖，甚至完全消灭了肿瘤。未观察到明显的心毒性和治疗相关的副作用。PDA@Lipo / DOX / ICG是一种基于PDA包覆的脂质体的多功能纳米平台，用于化疗和激光诱导PDT / PTT的准确和高效联用癌症治疗。©2023年陆等。

Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model.Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm2, 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed.PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.© 2023 Lu et al.