College of Biological and Pharmaceutical Sciences, China Three Gorges University, No.8 Daxue Road, Xiling District, Yichang, Hubei, 443002, P. R. China.
College of Chemistry and Molecular Sciences, Wuhan University N, o. 299, Bayi Road, Wuchang District, Wuhan, Hubei, 430000, P. R. China.
Chemistry. 2023 Jun 13;29(33):e202300861. doi: 10.1002/chem.202300861. Epub 2023 Apr 27.
Laser-free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep-seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA-responsive laser-free PDT was developed through metal-organic frameworks (MOFs)-mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)-loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)-mimicking hemin/G-quadruplex DNAzyme on MOFs. Simultaneously, the on-MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H O , thus allowing the CRET-mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self-illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA-amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic.
无激光光动力疗法（PDT）是一种有前途的深部肿瘤非侵入性治疗方式，但由于刺激策略有限，其效率受到限制。本文通过金属有机框架（MOFs）介导的化学发光共振能量转移（CRET）纳米平台，开发了一种新型 miRNA 响应型无激光 PDT。载光敏剂氯卟啉 e6（Ce6）的 MOFs 被发夹核酸功能化，通过催化发夹组装（CHA）对肿瘤生物标志物 miRNA 具有敏感的响应性，从而使辣根过氧化物酶（HRP）模拟血红素/G-四链体 DNA 酶在 MOFs 上的放大组装成为可能。同时，在存在鲁米诺和 H2O2 的情况下，在 MOF 上组装的 DNA 酶可有效地催化化学发光反应，从而刺激相邻的 Ce6，从而允许 CRET 介导的 Ce6 发光和活性氧（ROS）生成，以实现自照明 PDT。该 CRET 纳米平台在没有外部激光照射的情况下，实现了显著的恶性细胞凋亡和肿瘤抑制效果。可以预见，miRNA 放大的 CRET 纳米平台可能成为一种用于精确治疗的选择性和高效抗肿瘤纳米药物。
