Design and development of a mitochondrial-targeted photosensitizer for two-photon fluorescence imaging and photodynamic therapy

doi:10.1016/j.jmst.2022.09.022

J. Mater. Sci. Technol. ›› 2023, Vol. 141: 135-148.DOI: 10.1016/j.jmst.2022.09.022

• Research Article • Previous Articles Next Articles

Design and development of a mitochondrial-targeted photosensitizer for two-photon fluorescence imaging and photodynamic therapy

Yu Chen^a,c,1, Sheng Zhang^b,1, Tianjiao Cheng^b,1, Wei Lin^a,c, Linlin Mao^b, Zhonghui Chen^a,c, Yang Yang^d, Hanqing Huang^b, Jinqiu Li^a,c,*, Zhiyong Ke^b,d,**, Zhong-Kai Cui^b,**

^aInstitute of Cancer, Affiliated Hospital of Putian University, Putian University, Putian 351100, China;
^bDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;
^cAffiliated Putian Hospital of Southern Medical University, Putian 351100, China;
^dGuangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangzhou 510515, China

Received:2022-04-06 Revised:2022-09-20 Accepted:2022-09-28 Published:2023-04-01 Online:2022-11-02
Contact: *Institute of Cancer, Affiliated Hospital of Putian Uni- versity, Putian University, Putian 351100, China. **Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. E-mail addresses: lijinqiu0709@126.com (J. Li), kezhy@smu.edu.cn (Z. Ke), zhongkaicui@smu.edu.cn (Z.-K. Cui)
About author:1 These authors contributed equally to this work.

Abstract

Abstract: Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation. Mitochondria-specific photosensitizers have been reported to be critical for inducing cell apoptosis. Two-photon fluorescence imaging provides a new technique for delineating biological structures and activities in deep tissues. Herein, we developed a new aggregation-induced emission (AIE) active photosensitizer by attaching a pyridinium group for mitochondrial targeting. The rationally designed photosensitizer (TTTP) exhibited excellent photophysical properties, good biocompatibility, reactive oxygen species (ROS) stimulation ability, anticancer efficacy, and two-photon imaging properties. TTTP was highly taken up by cells and accumulated specifically in mitochondria but was selectively cytotoxic to cancer cells. Under light irradiation, the generation of ROS was significantly boosted, leading to actively induced apoptosis. The in vivo tumor photodynamic therapeutic efficacy of TTTP showed significant inhibition of tumor growth. Furthermore, the underlying mechanism of TTTP tumor suppression revealed that the apoptosis agonist Bax was markedly up-regulated while the antagonist Bcl-xL was down-regulated. This research provides a potential mitochondrial-targeted phototherapeutic agent for effective therapy and two-photon fluorescence imaging.

Key words: Mitochondrial-targeting, Two-photon fluorescence imaging, Photodynamic therapy, ApoptosisReactive oxygen species (ROS)

Yu Chen, Sheng Zhang, Tianjiao Cheng, Wei Lin, Linlin Mao, Zhonghui Chen, Yang Yang, Hanqing Huang, Jinqiu Li, Zhiyong Ke, Zhong-Kai Cui. Design and development of a mitochondrial-targeted photosensitizer for two-photon fluorescence imaging and photodynamic therapy[J]. J. Mater. Sci. Technol., 2023, 141: 135-148.

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Design and development of a mitochondrial-targeted photosensitizer for two-photon fluorescence imaging and photodynamic therapy

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