College of Veterinary Medicine, International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, China.
Department of Pathology, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou 450003, China.
ACS Appl Mater Interfaces. 2022 Mar 2;14(8):10092-10101. doi: 10.1021/acsami.1c23121. Epub 2022 Feb 16.
Photodynamic therapy (PDT) can eradicate cancer cells under light irradiation, mainly because of reactive singlet oxygen (O) being transformed from intratumoral oxygen. Nonetheless, the consumption of oxygen during PDT results in serious hypoxic conditions and an elevated hypoxia-inducing factor-1α (HIF-1α) level that hamper further photodynamic efficacy and induce tumor metastasis. To address this problem, we developed hypoxia-assisted NP-co-encapsulating Ce6 (photosensitizer) and YC-1 (HIF-1α inhibitor) as a self-rectifiable nanoinhibitor for synergistic antitumor treatment. PDT-aggravated intracellular hypoxic stress facilitated NP dissociation to release the drug (YC-1), which achieved tumor killing and HIF-1α inhibition to further enhance the therapeutic effect of PDT and prevent tumor metastasis. Besides, studies revealed that the HC/PI@YC-1 NPs afforded synergistic anticancer efficacy with minimal toxicity. Therefore, this study provides a prospective approach against PDT drawbacks and combination cancer therapy.
光动力疗法（PDT）可以在光照射下消灭癌细胞，这主要是因为肿瘤内氧气转化为活性单线态氧（O）。然而，PDT 过程中氧气的消耗会导致严重的缺氧状态和缺氧诱导因子-1α（HIF-1α）水平的升高，这会阻碍进一步的光动力疗效并诱导肿瘤转移。为了解决这个问题，我们开发了缺氧辅助的 NP 共包封 Ce6（光敏剂）和 YC-1（HIF-1α抑制剂）作为一种自修复的纳米抑制剂，用于协同抗肿瘤治疗。PDT 加重的细胞内缺氧应激促进了 NP 的解离以释放药物（YC-1），从而实现肿瘤杀伤和 HIF-1α抑制，进一步增强 PDT 的治疗效果并防止肿瘤转移。此外，研究表明 HC/PI@YC-1 NPs 具有协同抗癌功效且毒性最小。因此，本研究为克服 PDT 缺陷和联合癌症治疗提供了一种有前景的方法。
