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Title: Enhancing the Theranostic Performance of Organic Photosensitizers with Aggregation-Induced Emission
Authors: Kenry 
Liu, Bin 
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Materials Science, Multidisciplinary
Materials Science
Issue Date: 22-Jul-2022
Citation: Kenry, Liu, Bin (2022-07-22). Enhancing the Theranostic Performance of Organic Photosensitizers with Aggregation-Induced Emission. ACCOUNTS OF MATERIALS RESEARCH 3 (7). ScholarBank@NUS Repository.
Abstract: ConspectusPhotodynamic therapy has been actively explored recently to combat various physiological disorders and diseases, including bacterial infections, inflammation, and cancer. As a noninvasive modality with high spatiotemporal selectivity, photodynamic therapy leverages photosensitizers, light, and reactive oxygen species to induce cytotoxicity and cell death. Specifically, upon light irradiation, photosensitizers harvest the incident light energy to generate highly reactive singlet oxygen species through photochemical reactions to disrupt the integrity of certain cellular components of the target cells. The extent to which the target cells can be damaged depends largely on the characteristics of photosensitizers. As such, the selection and design of photosensitizers are essential to ensuring effective and safe photodynamic therapy. Unfortunately, organic photosensitizers typically used in photodynamic therapy tend to suffer from a considerable reduction in singlet oxygen production when these molecules aggregate, significantly limiting the efficacy of photodynamic therapy. To address this issue, a different class of organic photosensitizers with aggregation-induced emission (AIE) characteristics, which exhibit bright fluorescence and enhanced photosensitizing activity only when they exist in an aggregated state, has been increasingly formulated for disease theranostic applications.In general, AIE photosensitizers can be designed on the basis of several major strategies. For example, AIE photosensitizers with efficient singlet oxygen generation can be formulated by minimizing their singlet-triplet energy gap via tuning the distribution of the highest occupied molecular orbital and the lowest unoccupied molecular orbital of the molecules. Simultaneously, through donor-acceptor engineering, AIE photosensitizers can be designed to have increased molar absorptivity, red-shifted absorption and emission wavelengths, and improved body clearance. In situ click synthesis can also be adopted to formulate AIE photosensitizers with suppressed dark toxicity. These design approaches can be optimized using artificial intelligence or machine learning, leading to higher throughput discovery of AIE photosensitizers with exceptional performance. Intriguingly, the therapeutic impact of AIE photosensitizers can be further strengthened by modulating their performance-related features, notably targeting specificity, target accumulation and retention, tissue penetration depth, stimulus responsivity, and theranostic modality. By precisely controlling these elements, multifunctional and biocompatible AIE photosensitizers with superior performance can be realized.Herein, we describe our recent efforts in designing and formulating organic AIE photosensitizers with improved theranostic efficacy and safety to treat bacterial infections and cancer. We first introduce different principles that can be adopted to guide the design of AIE photosensitizers. We then present various ways to strengthen the different performance-associated features of AIE photosensitizers. These include enhancement of the targeting specificity, target accumulation, and retention of AIE photosensitizers through metabolic engineering, enhancement of the tissue penetration depth of AIE photosensitizers through chemiexcitation and ionizing irradiation, enhancement of AIE photosensitization by suppressing intrinsic oxidative resistance, enhancement of the responsivity of AIE photosensitizers through stimulus-responsive building blocks, and enhancement of the overall theranostic performance of AIE photosensitizers through combinatorial therapy. Finally, we identify current challenges, potential opportunities, and future research directions for this emerging field. Through this Account, we seek to stimulate further interest and active collaborations in the development, theranostic applications, and clinical translation of organic AIE photosensitizers to treat different diseases.
ISSN: 2643-6728
DOI: 10.1021/accountsmr.2c00039
Appears in Collections:Staff Publications

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