Photo-Activable Organosilver Nanosystem Facilitates Synergistic Cancer Theranostics.
Photo-Activable Organosilver Nanosystem Facilitates Synergistic Cancer Theranostics.
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DOI：
10.1021/acsami.2c21004
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发表时间：
2022-12
影响因子：
9.5
通讯作者：
Xiaohui Liu;Duo-Qing Fan;Yueming Ren;Shuai Huang;Jipeng Ding;Min Liu;S. Wegner;Jing Hou
中科院分区：
文献类型：
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作者：
Xiaohui Liu;Duo-Qing Fan;Yueming Ren;Shuai Huang;Jipeng Ding;Min Liu;S. Wegner;Jing Hou
抗癌药物的开发对人类健康很重要，但仍然是一个巨大的挑战。光动力疗法（PDT）通过光触发活性氧的产生来诱导癌细胞凋亡，是一种有前途的方法。然而，它在亚细胞靶向、缺氧微环境和深部恶性肿瘤方面的功效甚微。在这里，我们通过合理设计合成溶酶体靶向分子，构建了乳腺癌光激活治疗诊断纳米系统，该分子具有聚集诱导近红外（NIR）发射、光敏剂（PDT）和有机银（化疗）等多功能，用于近红外成像和协同癌症治疗。该合成分子可以自组装成纳米颗粒（TPIMBS NP），并用两亲性嵌段共聚物稳定，通过被动靶向增强在肿瘤部位的积累，同时减少正常组织中的渗漏。通过光化学内化，TPIMBS NPs优先富集在癌细胞的溶酶体中，并在光照射下产生活性氧（ROS），导致溶酶体破裂并将PSs释放到细胞质中，从而导致细胞凋亡。此外，TPIMBS NPs 光诱导释放 Ag+ 可以起到化疗作用，通过与 PDT 的协同作用显着提高整体治疗效果。这项研究为开发有效的癌症治疗方法提供了新的线索。
Anticancer drug development is important for human health, yet it remains a tremendous challenge. Photodynamic therapy (PDT), which induces cancer cell apoptosis via light-triggered production of reactive oxygen species, is a promising method. However, it has minimal efficacy in subcellular targeting, hypoxic microenvironments, and deep-seated malignancies. Here, we constructed a breast cancer photo-activable theranostic nanosystem through the rational design of a synthetic lysosomal-targeted molecule with multifunctions as aggregation-induced near-infrared (NIR) emission, a photosensitizer (PDT), and organosilver (chemotherapy) for NIR imaging and synergistic cancer therapy. The synthetic molecule could self-assemble into nanoparticles (TPIMBS NPs) and be stabilized with amphiphilic block copolymers for enhanced accumulation in tumor sites through passive targeting while reducing the leakage in normal tissues. Through photochemical internalization, TPIMBS NPs preferentially concentrated in the lysosomes of cancer cells and generated reactive oxygen species (ROS) upon light irradiation, resulting in lysosomal rupture and release of PSs to the cytosol, which led to cell apoptosis. Further, the photoinduced release of Ag+ from TPIMBS NPs could act as chemotherapy, significantly improving the overall therapeutic efficacy by synergistic effects with PDT. This research sheds fresh light on the creation of effective cancer treatments.