Mitochondria-targeting Type I AIE photosensitizer combined with H2S therapy: Uninterrupted hydroxyl radical generation for enhancing tumor therapy. (October 2022)

• Record Type: Journal Article
• Authors: Zhang, Tianfu; Liu, Zeming; Tang, Wenxue; Zhu, Daoming; Lyu, Meng; Lam, Jacky Wing Yip; Huang, Qinqin; Tang, Ben Zhong
• Is Part Of: Nano today. Volume 46(2022)
• Publication Date: 2022-10
• Subjects: Aggregation-induced emission -- Type I photosensitizer -- Hydrogen sulfide gas therapy -- Uninterrupted hydroxyl radical generation -- Injectable agarose hydrogels; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101620
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: Although Type I photosensitizers with aggregation-induced emission (AIE) characteristics have thrived as alternative tools for cancer photodynamic therapy (PDT) thanks to their efficient reactive oxygen species (ROS) generation and hypoxia resistance, accumulated reducing substances sinside the tumor and the short lifespan of ROS limit their therapeutic effects. How to continuously generate long-lasting ROS in tumors remains a thorny problem. Herein, we constructed an uninterrupted ROS generator by incorporating the H2 S donor, (NH4 )2 S, and a Type I AIE photosensitizer, TDCAc, into an injectable agarose hydrogel, namely TSH. Mitochondria-targeting TDCAc exhibited excellent performance in multi-model Type I photodynamic/photothermal therapy under near-infrared laser irradiation. While (NH4 )2 S generates H2 S gas in the acidic tumor microenvironment upon photothermal dissolution of TSH gel, which diffuses into cancer cells and effectively inhibits intracellular catalase activity. Thus, the intrinsic H2 O2 consumption pathway is blocked to promote endogenous labile iron pool-mediated continuous hydroxyl radical (·OH) generation in tumors. In both in vitro and in vivo experiments, uninterrupted massive production of·OH in cancer cells after laser irradiation of TSH gels was demonstrated. Notably, H2 S gas therapy is firstly combined with Type I AIE PDT, affording a novel synergistic strategy of continuous·OH generation for boosting tumor therapy. Graphical Abstract: ga1 Highlights: Firstly combined H2 S gas therapy with Type I AIE photosensitizer by a TSH hydrogel. AIE-active TDCAc nanoaggregate in TSH exhibited efficient Type I PDT/PTT. H2 S gas is released upon photothermal dissolution of TSH upon laser irradiation. The intracellular H2 O2 consumption pathway is blocked by H2 S gas therapy. Uninterrupted massive OH production was demonstrated for synergistic tumor therapy.