Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregationinduced emission (AIE) photosensitizers for photodynamic treatment of drugresistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant CTBZPyI exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers CTBZPyI with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a MRSA-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.

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Drug-resistant bacteria present a grave threat to human health. Photodynamic therapy (PDT) holds enormous potential as an innovative treatment for antimicrobial therapy. However, the generation of reactive oxygen species (ROS)...

In modern medicine, precision diagnosis and treatment using optical materials, such as fluorescence/photoacoustic imaging-guided photodynamic therapy (PDT), are becoming increasingly popular. Photosensitizers (PSs) are the most important component of PDT. Different from conventional PSs with planar molecular structures, which are susceptible to quenching effects caused by aggregation, the distinct advantages of AIE fluorogens open up new avenues for the development of image-guided PDT with improved treatment accuracy and efficacy in practical applications. It is critical that as much of the energy absorbed by optical materials is dissipated into the pathways required to maximize biomedical applications as possible. Intersystem crossing (ISC) represents a key step during the energy conversion process that determines many fundamental optical properties, such as increasing the efficiency of reactive oxygen species (ROS) production from PSs, thus enhancing PDT efficacy. Although some review articles have summarized the accomplishments of various optical materials in imaging and therapeutics, few of them have focused on how to improve the phototherapeutic applications, especially PDT, by adjusting the ISC process of organic optics materials. In this review, we emphasize the latest advances in the reasonable design of AIE-active PSs with type I photochemical mechanism for anticancer or antibacterial applications based on ISC modulation, as well as discuss the future prospects and challenges of them. In order to maximize the anticancer or antibacterial effects of type I AIE PSs, it is the aim of this review to offer advice for their design with the best energy conversion.

X‐ray induced photodynamic therapy (X‐PDT) circumvents the poor penetration depth of conventional PDT with minimal radio‐resistance generation. However, conventional X‐PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation‐induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X‐ray irradiation is reported for hypoxia‐tolerant X‐PDT. Heteroatoms are introduced to enhance X‐ray harvesting and ROS generation ability, and AIE‐active TBDCR exhibits aggregation‐enhanced ROS especially less oxygen‐dependent hydroxyl radical (HO•−, type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near‐infrared fluorescence and massive singlet oxygen and HO•− generation under direct X‐ray irradiation, which demonstrate excellent antitumor X‐PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1O2 and radicals (HO•−) in response to direct X‐ray irradiation, which shall provide new insights for designing organic scintillators with excellent X‐ray harvesting and predominant free radical generation for efficient X‐PDT.