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Issue 13, 2020
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Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress

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Abstract

Photodynamic therapy (PDT) is considered a pioneering and effective modality for cancer treatment, but it is still facing challenges of hypoxic tumors. Recently, Type I PDT, as an effective strategy to address this issue, has drawn considerable attention. Few reports are available on the capability for Type I reactive oxygen species (ROS) generation of purely organic photosensitizers (PSs). Herein, we report two new Type I PSs, α-TPA-PIO and β-TPA-PIO, from phosphindole oxide-based isomers with efficient Type I ROS generation abilities. A detailed study on photophysical and photochemical mechanisms is conducted to shed light on the molecular design of PSs based on the Type I mechanism. The in vitro results demonstrate that these two PSs can selectively accumulate in a neutral lipid region, particularly in the endoplasmic reticulum (ER), of cells and efficiently induce ER-stress mediated apoptosis and autophagy in PDT. In vivo models indicate that β-TPA-PIO successfully achieves remarkable tumor ablation. The ROS-based ER stress triggered by β-TPA-PIO-mediated PDT has high potential as a precursor of the immunostimulatory effect for immunotherapy. This work presents a comprehensive protocol for Type I-based purely organic PSs and highlights the significance of considering the working mechanism in the design of PSs for the optimization of cancer treatment protocols.

Graphical abstract: Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress

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Supplementary files

Article information


Submitted
10 Feb 2020
Accepted
20 Feb 2020
First published
02 Mar 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 3405-3417
Article type
Edge Article

Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress

Z. Zhuang, J. Dai, M. Yu, J. Li, P. Shen, R. Hu, X. Lou, Z. Zhao and B. Z. Tang, Chem. Sci., 2020, 11, 3405
DOI: 10.1039/D0SC00785D

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    [Original citation] - Published by The Royal Society of Chemistry.

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