Issue 15, 2024

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy

Abstract

Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O2˙, while phenyl S-rhodamine results in O2˙ and 1O2 through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O2˙. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.

Graphical abstract: Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy

Supplementary files

Article information

Article type
Paper
Submitted
15 1 2024
Accepted
25 3 2024
First published
26 3 2024

J. Mater. Chem. B, 2024,12, 3686-3693

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy

J. Liang, X. Ran, Y. Liu, X. Yu, S. Chen and K. Li, J. Mater. Chem. B, 2024, 12, 3686 DOI: 10.1039/D4TB00099D

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