Good Steel Used in the Blade: Well‐Tailored Type‐I Photosensitizers with Aggregation‐Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy. Issue 14 (21st May 2021)

• Record Type: Journal Article
• Authors: Kang, Miaomiao; Zhang, Zhijun; Xu, Wenhan; Wen, Haifei; Zhu, Wei; Wu, Qian; Wu, Hongzhuo; Gong, Junyi; Wang, Zhijia; Wang, Dong; Tang, Ben Zhong
• Is Part Of: Advanced science. Volume 8:Issue 14(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-21
• Subjects: aggregation‐induced emission -- nuclear targeting -- photodynamic therapy -- type‐I photosensitizer; Science -- Periodicals; 505
• DOI: 10.1002/advs.202100524
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high‐performance less‐oxygen‐dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type‐I PSs with aggregation‐induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type‐I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid‐activated TAT‐peptide‐modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride‐modified TAT, the corresponding TTFMN‐loaded nanoparticles accompanied with acid‐triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type‐I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate "Good Steel Used in the Blade" tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine. Abstract : A precise nuclear targeting photodynamic therapy (PDT) protocol based on tactfully designed type‐I photosensitizers with aggregation‐induced emission characteristics is fabricated for the first time with the aid of a lysosomal acid‐activated TAT‐modified nuclear delivery system, which can significantly maximize the PDT efficacy. ​