Fluorescence imaging-guided photodynamic therapy (FIG-PDT) holds promise for cancer treatment, yet challenges persist in poor imaging quality, phototoxicity, and insufficient anti-tumor effect. Herein, a novel nanoplatform, LipoHPM, designed to address these challenges, is reported. This approach employs an acid-sensitive amine linker to connect a biotin-modified hydrophilic polymer (^BiotinPEG) with a new hydrophobic photosensitizer (MBA), forming OFF-state ^BiotinPEG-MBA (PM) micelles via an aggregation-caused quenching (ACQ) effect. These micelles are then co-loaded with the tumor penetration enhancer hydralazine (HDZ) into pH-sensitive liposomes (LipoHPM). Leveraging the ACQ effect, LipoHPM is silent in both fluorescence and reactive oxygen species (ROS) generation during blood circulation but restores both properties upon disassembly. Following intravenous injection in tumor-bearing mice, LipoHPM actively targets tumor cells overexpressing biotin-receptors, contributing to enhanced tumor accumulation. Upon cellular internalization, LipoHPM disassembles within lysosomes, releasing HDZ to enhance tumor penetration and inhibit tumor metastasis. Concurrently, the micelles activate fluorescence for tumor imaging and boost the production of both type-I and type-II ROS for tumor eradication. Therefore, the smart LipoHPM synergistically integrates near-infrared emission, activatable tumor imaging, robust ROS generation, efficient anti-tumor and anti-metastasis activity, successfully overcoming limitations of conventional photosensitizers and establishing itself as a promising nanoplatform for potent FIG-PDT applications.

中文翻译：

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智能纳米组装实现可激活的近红外荧光和 ROS 生成，增强肿瘤穿透力，用于成像引导光动力治疗

荧光成像引导光动力疗法（FIG-PDT）有望用于癌症治疗，但仍面临成像质量差、光毒性和抗肿瘤效果不足等问题。本文报道了一种新型纳米平台 LipoHPM，旨在解决这些挑战。该方法采用酸敏感胺连接体将生物素修饰的亲水性聚合物（^生物素PEG）与新型疏水性光敏剂（MBA）连接，通过聚集引起的猝灭形成关闭状态的^生物素PEG - MBA (PM) 胶束（ACQ）效应。然后将这些胶束与肿瘤渗透增强剂肼苯达嗪 ( H DZ)共同装载到 pH 敏感脂质体 (Lipo HPM ) 中。利用 ACQ 效应，LipoHPM 在血液循环过程中不会产生荧光和活性氧 (ROS)，但在分解后会恢复这两种特性。在对荷瘤小鼠进行静脉注射后，LipoHPM 主动靶向过度表达生物素受体的肿瘤细胞，从而促进肿瘤积累。细胞内化后，LipoHPM 在溶酶体内分解，释放 HDZ 以增强肿瘤渗透并抑制肿瘤转移。同时，胶束激活荧光以进行肿瘤成像，并促进 I 型和 II 型 ROS 的产生以消除肿瘤。因此，智能LipoHPM协同集成了近红外发射、可激活肿瘤成像、强大的ROS生成、高效的抗肿瘤和抗转移活性，成功克服了传统光敏剂的局限性，并将其自身打造成一个有前途的FIG-PDT应用的纳米平台。