Self-Rectifiable and Hypoxia-Assisted Chemo-Photodynamic Nanoinhibitor for Synergistic Cancer Therapy
Self-Rectifiable and Hypoxia-Assisted Chemo-Photodynamic Nanoinhibitor for Synergistic Cancer Therapy
复制标题
用于协同癌症治疗的自整流和缺氧辅助化学光动力纳米抑制剂
DOI：
10.1021/acsami.1c23121
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发表时间：
2022
影响因子：
9.5
通讯作者：
Zhang Gaiping
中科院分区：
文献类型：
--
作者：
Wang Yanan;Huo Jian;Li Shuang;Huang Ran;Fan Daopeng;Cheng Hanghang;Wan Bo;Du Yongkun;He Hua;Zhang Gaiping
光动力疗法(PDT)可以在光照射下消灭癌细胞，主要是由于瘤内氧转化为活性单线态氧(1O2)所致。然而，光动力治疗过程中的氧气消耗会导致严重的低氧条件和缺氧诱导因子-1α(HIF-1α)水平的升高，从而阻碍进一步的光动力效应并诱导肿瘤转移。为了解决这个问题，我们开发了低氧辅助的NP共包裹Ce6(光敏剂)和YC-1(HIF-1α抑制剂)作为一种可自我纠正的纳米抑制剂，用于协同抗肿瘤治疗。光动力加重的细胞内低氧应激促进NP解离释放药物YC-1，从而达到杀瘤和抑制缺氧诱导因子-1α的目的，从而进一步提高光动力的治疗效果，防止肿瘤转移。此外，活体研究表明，HC/PI@YC-1纳米粒具有协同抗癌作用，毒性最小。因此，这项研究为克服光动力疗法的缺陷和联合治疗癌症提供了一种前瞻性的方法。
Photodynamic therapy (PDT) can eradicate cancer cells under light irradiation, mainly because of reactive singlet oxygen (1O2) 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,in vivostudies 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.