Photochemical and Biological Dual-Effects Enhance the Inhibition of Photosensitizers for Tumour Growth

Authors

Huiyu Niu
Yang Liu
Yafu Wang
Yonggang Yang
Ge Wang
Tony D James
Jonathan L Sessler
Hua Zhang

Language

English

Publication Date

5-22-2024

Journal

Chemical Science

DOI

10.1039/d4sc00874j

PMID

38784735

PMCID

PMC11110147

PubMedCentral® Posted Date

4-25-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Photosensitizers typically rely on a singular photochemical reaction to generate reactive oxygen species, which can then inhibit or eradicate lesions. However, photosensitizers often exhibit limited therapeutic efficiency due to their reliance on a single photochemical effect. Herein, we propose a new strategy that integrates the photochemical effect (type-I photochemical effect) with a biological effect (proton sponge effect). To test our strategy, we designed a series of photosensitizers (ZZ-sers) based on the naphthalimide molecule. ZZ-sers incorporate both a p-toluenesulfonyl moiety and weakly basic groups to activate the proton sponge effect while simultaneously strengthening the type-I photochemical effect, resulting in enhanced apoptosis and programmed cell death. Experiments confirmed near-complete eradication of the tumour burden after 14 days (Wlight/Wcontrol ≈ 0.18, W represents the tumour weight). These findings support the notion that the coupling of a type-I photochemical effect with a proton sponge effect can enhance the tumour inhibition by ZZ-sers, even if the basic molecular backbones of the photosensitizers exhibit nearly zero or minimal tumour inhibition ability. We anticipate that this strategy can be generalized to develop additional new photosensitizers with improved therapeutic efficacy while overcoming limitations associated with systems relying solely on single photochemical effects.

Published Open-Access

yes

Recommended Citation

Niu, Huiyu; Liu, Yang; Wang, Yafu; et al., "Photochemical and Biological Dual-Effects Enhance the Inhibition of Photosensitizers for Tumour Growth" (2024). Faculty, Staff and Student Publications. 6186.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6186