A photoactivatable theranostic probe for simultaneous oxidative stress-triggered multi-color cellular imaging and photodynamic therapy

Xiaohui Chen; Zicong Zhang; Wenshuai Luo; Zeyan Zhuang; Zujin Zhao; Lei Wang; Dong Wang; Ben Zhong Tang

doi:10.1016/j.biomaterials.2022.121680

A photoactivatable theranostic probe for simultaneous oxidative stress-triggered multi-color cellular imaging and photodynamic therapy

Biomaterials. 2022 Aug:287:121680. doi: 10.1016/j.biomaterials.2022.121680. Epub 2022 Jul 14.

Authors

Xiaohui Chen¹, Zicong Zhang², Wenshuai Luo³, Zeyan Zhuang⁴, Zujin Zhao⁴, Lei Wang³, Dong Wang⁵, Ben Zhong Tang⁶

Affiliations

¹ Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China; Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
² School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, China.
³ Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China.
⁴ Center for Aggregation-Induced Emission, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640, China.
⁵ Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address: wangd@szu.edu.cn.
⁶ School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, China; Center for Aggregation-Induced Emission, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640, China. Electronic address: tangbenz@cuhk.edu.cn.

PMID: 35872556
DOI: 10.1016/j.biomaterials.2022.121680

Abstract

Simultaneous in situ monitoring critical organelles upon oxidative stress and implementing therapeutics utilizing oxidative stress are of vital importance and remain challenging task. Herein, we rationally design and facilely synthesized a photoactivatable fluorescent probe bearing 1,4-dihydropyridine moiety with aggregation-induced emission (AIE) tendency, namely TPA-DHPy, which can rapidly transform into its pyridine counterpart TPA-Py via photo-oxidative dehydrogenation showing strong polarity sensitivity and largely red-shifted emission. TPA-DHPy- and TPA-Py-based type I/type II photosensitization is able to effectively generate reactive oxygen species to induce in situ oxidative stress under white light irradiation. TPA-DHPy can be taken up by cancer cells, and gradually light up lipid droplets (LDs) and endoplasmic reticulum (ER) during photoactivatable process, as well as in situ monitoring difference and alteration of their microenvironment upon oxidative stress by means of multi-color fluorescence imaging in lambda mode. Furthermore, the in situ generated TPA-Py is capable of further destroying the functions of LDs and ER with prolonging the irradiation time, and remarkably inhibiting tumor growth under white light irradiation by the way of photodynamic therapy. This study thus offers useful insights into designing a new generation of theranostic agents towards imaging-guided precise cancer therapy.

Keywords: Aggregation-induced emission; Multi-color cellular imaging; Photoactivation; Photodynamic therapy.