Precise Molecular Engineering of Type I Photosensitizers with Near‐Infrared Aggregation‐Induced Emission for Image‐Guided Photodynamic Killing of Multidrug‐Resistant Bacteria

Abstract

Multidrug resistance (MDR) bacteria pose a serious threat to human health. The development of alternative treatment modalities and therapeutic agents for treating MDR bacteria-caused infections remains a global challenge. Herein, a series of near-infrared (NIR) anion-𝝅 + photosensitizers featuring aggregation-induced emission (AIE-PSs) are rationally designed and successfully developed for broad-spectrum MDR bacteria eradication. Due to the strong intramolecular charge transfer (ICT) and enhanced highly efficient intersystem crossing (ISC), these electron-rich anion-𝝅 + AIE-PSs show boosted type I reactive oxygen species (ROS) generation capability involving hydroxyl radicals and superoxide anion radicals, and up to 99% photodynamic killing efficacy is achieved for both Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Escherichia coli (MDR E. coli) under a low dose white light irradiation (16 mW cm −2 ). In vivo experiments confirm that one of these AIE-PSs exhibit excellent therapeutic performance in curing MRSA or MDR E. coli-infected wounds with negligible side-effects. The study would thus provide useful guidance for the rational design of high-performance type I AIE-PSs to overcome antibiotic resistance.

Rational design of a meso phosphate-substituted pyronin as a type I photosensitizer for photodynamic therapy

“…Up to now, some strategies have been successfully developed to achieve type I PDT with organic PSs, such as improving the rate constant ( k ISC ) of intersystem crossing (ISC) to generate triplet excitons, 13–15 enhancing intramolecular charge transfer (ICT) to reduce the energy gap (Δ EST ) between the singlet and triplet states, 16–18 and expanding the spin–orbit coupling (SOC) constant by introducing heavy atoms. 19,20 Although significant progress has been made, there is always a high demand to develop hypoxia-resistant type I PSs.…”

Type I Photosensitizers Based on Aggregation-Induced Emission: A Rising Star in Photodynamic Therapy

“…In this respect, type I PDT has been widely employed due to the longer half-life of O 2 •− , as well as the strong oxidizing property of OH • . Possessing the advantage of AIE and AIG-ROS, periodical achievements in the FLI-guided PDT of pathogenic microbes have been attained, based on AIE-active type I PSs [ 74 , 75 , 76 ].…”

Near-Infrared-Emissive AIE Bioconjugates: Recent Advances and Perspectives

“…Tang et al, prepared a novel antimicrobial drug by the bioconjugation of AIEgens and phage, which can realize the specific imaging and killing of P. aeruginosa [95]. As one kind of virus, phage can target its hosts (including bacteria, fungi, algae, and others) with superb specificity and then attack them [96]. In view of the superiorities of AIEgens in microbial detection and therapy demonstrated by substantial studies, the AIEgen-phage bioconjugate is considered as a win-win integration [97].…”