Stereoisomeric Engineering of Aggregation-induced Emission Photosensitizers Towards Fungal Killing

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Nov 17

PMID 36396937

Authors

Wenping Zhu

Ying Li

Shaoxun Guo

Wu-Jie Guo

Tuokai Peng

Hui Li

Bin Liu

Hui-Qing Peng

Ben Zhong Tang

Affiliations

Soon will be listed here.

Abstract

Fungal infection poses and increased risk to human health. Photodynamic therapy (PDT) as an alternative antifungal approach garners much interest due to its minimal side effects and negligible antifungal drug resistance. Herein, we develop stereoisomeric photosensitizers ((Z)- and (E)-TPE-EPy) by harnessing different spatial configurations of one molecule. They possess aggregation-induced emission characteristics and ROS, viz. O and O generation capabilities that enable image-guided PDT. Also, the cationization of the photosensitizers realizes the targeting of fungal mitochondria for antifungal PDT killing. Particularly, stereoisomeric engineering assisted by supramolecular assembly leads to enhanced fluorescence intensity and ROS generation efficiency of the stereoisomers due to the excited state energy flow from nonradiative decay to the fluorescence pathway and intersystem (ISC) process. As a result, the supramolecular assemblies based on (Z)- and (E)-TPE-EPy show dramatically lowered dark toxicity without sacrificing their significant phototoxicity in the photodynamic antifungal experiments. This study is a demonstration of stereoisomeric engineering of aggregation-induced emission photosensitizers based on (Z)- and (E)-configurations.

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References

Zhang L, Yan K, Zhang Y, Huang R, Bian J, Zheng C . High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc Natl Acad Sci U S A. 2007; 104(11):4606-11. PMC: 1838648. DOI: 10.1073/pnas.0609370104. View

Peng H, Liu B, Liu J, Wei P, Zhang H, Han T . "Seeing" and Controlling Photoisomerization by ()-/()-Isomers with Aggregation-Induced Emission Characteristics. ACS Nano. 2019; 13(10):12120-12126. DOI: 10.1021/acsnano.9b06578. View

Li Q, Li Y, Min T, Gong J, Du L, Lee Phillips D . Time-Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE-Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation. Angew Chem Int Ed Engl. 2019; 59(24):9470-9477. DOI: 10.1002/anie.201909706. View

Kong H, Segre J . Cultivating fungal research. Science. 2020; 368(6489):365-366. PMC: 10506662. DOI: 10.1126/science.aaz8086. View

Huang Z, Chen X, ONeill S, Wu G, Whitaker D, Li J . Highly compressible glass-like supramolecular polymer networks. Nat Mater. 2021; 21(1):103-109. DOI: 10.1038/s41563-021-01124-x. View

Fang F, Yuan Y, Wan Y, Li J, Song Y, Chen W . Near-Infrared Thermally Activated Delayed Fluorescence Nanoparticle: A Metal-Free Photosensitizer for Two-Photon-Activated Photodynamic Therapy at the Cell and Small Animal Levels. Small. 2022; 18(6):e2106215. DOI: 10.1002/smll.202106215. View

McLellan C, Vincent B, Solis N, Lancaster A, Sullivan L, Hartland C . Inhibiting mitochondrial phosphate transport as an unexploited antifungal strategy. Nat Chem Biol. 2017; 14(2):135-141. PMC: 5771894. DOI: 10.1038/nchembio.2534. View

Break T, Oikonomou V, Dutzan N, Desai J, Swidergall M, Freiwald T . Aberrant type 1 immunity drives susceptibility to mucosal fungal infections. Science. 2021; 371(6526). PMC: 8326743. DOI: 10.1126/science.aay5731. View

Teng K, Chen W, Niu L, Fang W, Cui G, Yang Q . BODIPY-Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen. Angew Chem Int Ed Engl. 2021; 60(36):19912-19920. DOI: 10.1002/anie.202106748. View

10.

Mao D, Hu F, Yi Z, Kenry , Xu S, Yan S . AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation. Sci Adv. 2020; 6(26):eabb2712. PMC: 7319755. DOI: 10.1126/sciadv.abb2712. View

11.

Healey K, Zhao Y, Perez W, Lockhart S, Sobel J, Farmakiotis D . Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nat Commun. 2016; 7:11128. PMC: 5603725. DOI: 10.1038/ncomms11128. View

12.

Peng H, Zheng X, Han T, Kwok R, Lam J, Huang X . Dramatic Differences in Aggregation-Induced Emission and Supramolecular Polymerizability of Tetraphenylethene-Based Stereoisomers. J Am Chem Soc. 2017; 139(29):10150-10156. DOI: 10.1021/jacs.7b05792. View

13.

Sun W, Ma X, Wang H, Du Y, Chen J, Hu H . MYO1F regulates antifungal immunity by regulating acetylation of microtubules. Proc Natl Acad Sci U S A. 2021; 118(30). PMC: 8325298. DOI: 10.1073/pnas.2100230118. View

14.

Zhou W, Chen Y, Yu Q, Zhang H, Liu Z, Dai X . Ultralong purely organic aqueous phosphorescence supramolecular polymer for targeted tumor cell imaging. Nat Commun. 2020; 11(1):4655. PMC: 7494876. DOI: 10.1038/s41467-020-18520-7. View

15.

Hu F, Xu S, Liu B . Photosensitizers with Aggregation-Induced Emission: Materials and Biomedical Applications. Adv Mater. 2018; 30(45):e1801350. DOI: 10.1002/adma.201801350. View

16.

An J, Tang S, Hong G, Chen W, Chen M, Song J . An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers. Nat Commun. 2022; 13(1):2225. PMC: 9038921. DOI: 10.1038/s41467-022-29862-9. View

17.

Wang H, Xue K, Yang Y, Hu H, Xu J, Zhang X . In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity. J Am Chem Soc. 2022; 144(5):2360-2367. DOI: 10.1021/jacs.1c13067. View

18.

Dolmans D, Fukumura D, Jain R . Photodynamic therapy for cancer. Nat Rev Cancer. 2003; 3(5):380-7. DOI: 10.1038/nrc1071. View

19.

Teng K, Niu L, Yang Q . A host-guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator. Chem Sci. 2022; 13(20):5951-5956. PMC: 9132067. DOI: 10.1039/d2sc01469f. View

20.

Wang J, Huang Z, Ma X, Tian H . Visible-Light-Excited Room-Temperature Phosphorescence in Water by Cucurbit[8]uril-Mediated Supramolecular Assembly. Angew Chem Int Ed Engl. 2019; 59(25):9928-9933. DOI: 10.1002/anie.201914513. View