Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
Key Lab of Resource Chemistry of MOE & Shanghai Key Lab of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R. China.
Nanoscale. 2022 Jun 30;14(25):9097-9103. doi: 10.1039/d2nr01122k.
Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, which was capable of mitochondria-targeted co-delivery of the cysteine protease inhibitor and carbon monoxide (CO) stimulated with an 808 nm near infrared (NIR) laser. Nanoplatform (1) was prepared by covalent attachment of a mitochondria-targeted CO donor (TPPMnCO) and a Ru(II)-caged cysteine protease inhibitor (Ru-inhibitor) on the surface of fluorescent N-doped graphene quantum dots (N-GQDs). Nanoplatform (1) preferentially accumulated in the mitochondria of cancer cells and instantly delivered CO and the cysteine protease inhibitor upon 808 nm NIR light irradiation, thus damaging mitochondria and leading to significant and anticancer efficacy. In addition, nanoplatform (1) has good biocompatibility and did not exert any toxic side effects on mice during the period of treatment. The targeted subcellular mitochondrial co-delivery of CO and the cysteine protease inhibitor may provide new insights into CO and enzyme inhibitor combined therapies for cancer treatment.
光动力化疗因其能够克服肿瘤组织缺氧的缺点，与传统光动力疗法相比，引起了广泛的关注。在这项工作中，设计并制备了新型多功能纳米平台（1），Ru 抑制剂@TPPMnCO@N-GQDs，它能够在 808nm 近红外（NIR）激光的刺激下，实现靶向线粒体的半胱氨酸蛋白酶抑制剂和一氧化碳（CO）的共递运。纳米平台（1）通过将靶向线粒体的 CO 供体（TPPMnCO）和 Ru(II)封闭的半胱氨酸蛋白酶抑制剂（Ru-抑制剂）共价连接到荧光氮掺杂石墨烯量子点（N-GQDs）的表面来制备。纳米平台（1）优先聚集在癌细胞的线粒体中，并在 808nmNIR 光照射下瞬间递运 CO 和半胱氨酸蛋白酶抑制剂，从而损伤线粒体，导致显著的抗肿瘤疗效。此外，纳米平台（1）具有良好的生物相容性，在治疗期间对小鼠没有任何毒副作用。靶向亚细胞线粒体共递运 CO 和半胱氨酸蛋白酶抑制剂可能为癌症治疗中 CO 和酶抑制剂联合治疗提供新的思路。
