Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.

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.

• Authors: Miaomiao Kang, Zhijun Zhang, Wenhan Xu, Haifei Wen, Wei Zhu, Qian Wu, Hongzhuo Wu, Junyi Gong, Zhijia Wang, Dong Wang, Ben Zhong Tang
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 14 Pg. e2100524 (07 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34021726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Photosensitizing Agents
• Polymers
• Reactive Oxygen Species

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Disease Models, Animal
• Fluorescence
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms (drug therapy)
• Photochemotherapy (methods)
• Photosensitizing Agents (therapeutic use)
• Polymers (chemistry)
• Reactive Oxygen Species (metabolism)