Hypoxia‐Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 19; no. 1; pp. e2205440 - n/a
• Main Authors: Tang, Yuqi, Wang, Xing, Zhu, Guanqun, Liu, Zhiyang, Chen, Xu‐Man, Bisoyi, Hari Krishna, Chen, Xiao, Chen, Xiaofei, Xu, Yiyi, Li, Juping, Li, Quan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.01.2023
• Subjects: aggregation‐induced emission; Fluorescence; fluorescence on and off; Humans; Hypoxia; hypoxia‐responsive; Lipids; Lysosomes; Nanotechnology; Neoplasms - drug therapy; Neoplasms - pathology; Organelles; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Tumors; aggregation-induced emission; fluorescence on and off; tumors; hypoxia-responsive; photodynamic therapy
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202205440

Developing safe and precise image‐guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia‐responsive photosensitizer, TPA‐Azo. Introducing the azo group into the photosensitizer TPA‐BN with aggregation‐induced emission quenches its fluorescence. When the nonfluorescent TPA‐Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA‐BN with an amino group that exhibits fluorescence‐activatable image‐guided photodynamic therapy with dual‐organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence‐activatable photosensitizers. When the nonfluorescent hypoxia‐responsive photosensitizer TPA‐Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate the fluorescent photosensitizer TPA‐BN with the aggregation‐induced emission property, which can realize the fluorescence‐activatable image‐guided photodynamic therapy with dual‐organelle (lipid droplets and lysosomes) targeting.