Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

中文翻译：

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用于增强乳腺癌光动力治疗的线粒体靶向和自供氧偏心空心纳米平台

光动力疗法（PDT）因其微创性和时空选择性而在肿瘤治疗中受到越来越多的关注。然而，光敏剂的靶向性差和肿瘤微环境的缺氧限制了PDT的疗效。本文通过各向异性封装和水热蚀刻制备偏心中空介孔有机二氧化硅纳米颗粒（EHMON），用于构建具有靶向和缓氧特性的PDT纳米平台。制备的EHMONs具有独特的偏心中空结构、均匀的尺寸（300 nm）、大的空腔和有序的介孔通道（2.3 nm）。EHMON 使用线粒体靶向分子三苯膦 (CTPP) 和光敏剂二氢卟酚 e6 (Ce6) 进行修饰。EHMON 的内腔进一步装载了载氧化合物全氟化碳 (PFC)。溶血实验和体外毒性实验表明，EHMONs-Ce6-CTPP具有非常好的生物相容性，可以靶向三阴性乳腺癌的线粒体，从而增加进入癌细胞后光敏剂Ce6在线粒体的积累。具有携氧能力的EHMONs-Ce6-CTPP@PFCs进入癌细胞后可以缓解缺氧。模型和细胞实验表明，EHMONs-Ce6-CTPP@PFCs 产生更多的单线态氧活性氧（ROS）。因此，体外和体内实验表明EHMONs-Ce6-CTPP@PFCs对三阴性乳腺癌显示出优异的治疗效果。这项研究为靶向和载氧纳米平台增强 PDF 有效性提供了一种新方法。