Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, PR China.
Dongguan Key Laboratory of Drug Design and Formulation Technology, Key Laboratory for Nanomedicine, Guangdong Medical University, Dongguan 523808, PR China.
ACS Appl Mater Interfaces. 2020 Mar 18;12(11):12573-12583. doi: 10.1021/acsami.0c00921. Epub 2020 Mar 10.
Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze HO and tumor-overexpressed HO in situ generating sufficient ROS. TiOP can photosplit water to produce ·OH radical, HO, and O. Generated O not only conquers the hypoxia of tumor environment but also can be further excited by TiOP to O for killing tumor cells. Density functional theory calculations indicate that high energy in excited state (S) of TiOP and narrow gap energy between S and the triplet excited state (T) might contribute to the efficient photocatalytic action. Moreover, the generated and overexpressed HO in tumors can also be photocatalyzed to generate O especially in acid condition, helpful to specific anticancer effect while harmless to normal tissues. This research might pave a new way to bypass the hypoxia-triggered problem for cancer therapy.
活性氧（ROS）介导的细胞凋亡已成为肿瘤氧化损伤的重要策略，而肿瘤缺氧是提高效率的主要瓶颈。在这里，通过将 TiO-卟啉（TiOP）封装在叶酸脂质体中，设计了一种新型的 TiO-卟啉纳米系统（FA-TiOPs）。该纳米系统可以在光催化下原位产生足够的 ROS，催化 HO 和肿瘤过表达的 HO。TiOP 可以光解水产生·OH 自由基、HO 和 O。生成的 O 不仅克服了肿瘤环境的缺氧，而且还可以被 TiOP 进一步激发到 O 以杀死肿瘤细胞。密度泛函理论计算表明，TiOP 的激发态（S）中的高能和 S 与三重激发态（T）之间的窄能隙可能有助于有效的光催化作用。此外，肿瘤中产生和过表达的 HO 也可以被光催化生成 O，特别是在酸性条件下，有助于实现特异性抗癌作用，而对正常组织无害。这项研究可能为癌症治疗中绕过缺氧触发问题开辟了一条新途径。
