Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies for constructing phototheranostic systems by engineering the integration of photosensitizers (PSs) into nanosystems, nano‐PSs face challenges including complexity in the preparation process, low delivery efficiency, and potential toxicity issues. Contrastingly, the burgeoning popularity of small molecule PSs characterized by aggregation‐induced emission (AIE) has become evident in the arena of cancer phototheranostics. This preference is underscored by their well‐defined structures, adjustable photophysical properties, and low toxicity. Therefore, acquiring profound insights into the pioneering strides achievable through a solitary small molecule PS with AIE in tumor phototheranostics is of paramount scientific significance. In this review, we will discuss the recent progress of small molecule PSs with AIE properties in cancer diagnosis and phototherapies with representative examples, guided by the ethos of “Complexity made easy”. We also look forward to the future development direction of AIE small molecules, with a central objective of advancing cancer research through a focal emphasis on simplicity, expeditiousness, and safety.

Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP‐QY has a high molar absorption coefficient and an excellent ability to generate ¹O₂ and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP‐QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP‐QY‐mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole‐resistant strains. Moreover, TBTCP‐QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.

Dental caries is among the most prevalent dental diseases globally, which arises from the formation of microbial biofilm on teeth. Besides, tooth whitening represents one of the fastest‐growing areas of cosmetic dentistry. It will thus be great if tooth biofilm eradication can be combined with tooth whitening. Herein, a highly efficient photodynamic dental therapy strategy is reported for tooth biofilm eradication and tooth discoloration by employing a photosensitizer (DTTPB) with aggregation‐induced emission characteristics. DTTPB can efficiently inactivate S. mutans, and inhibit biofilm formation by suppressing the expression of genes associated with extracellular polymeric substance synthesis, bacterial adhesion, and superoxide reduction. Its inhibition performance can be further enhanced through combined treatment with chlorhexidine. Besides, DTTPB exhibits an excellent tooth‐discoloration effect on both colored saliva‐coated hydroxyapatite and clinical teeth, with short treatment time (less than 1 h), better tooth‐whitening performance than 30% hydrogen peroxide, and almost no damage to the teeth. DTTPB also demonstrates excellent biocompatibility with neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications for simultaneous tooth biofilm eradication and tooth whitening in clinical dentistry.

Photodynamic therapy (PDT), which relies on the activation of photosensitizers by specific wavelengths of light to generate reactive oxygen species (ROS) for targeted pathogen or diseased tissue eradication, offers substantial promise for clinical wound management. However, its application in diabetic wound management remains constrained by suboptimal therapeutic efficacy, recurrent infections, treatment-associated pain, scar formation, and dependence on costly specialized equipment. Here, we present a sunlight-activated nanospray formulation comprising chitosan oligosaccharide-coated nanoparticles (SPS), engineered for the rapid and effective management of diabetic wounds in outdoor and resource-limited settings. SPS enables efficient ROS generation under ambient natural light, thereby reducing treatment-associated discomfort while maintaining effective photodynamic antimicrobial action. Additionally, the chitosan oligosaccharide coating confers intrinsic hemostatic, antibacterial, and antioxidative properties that synergistically accelerate wound closure and reduce the risk of scarring. The topical spray delivery circumvents systemic phototoxicity, improving patient compliance and broadening the accessibility of PDT. This strategy effectively overcomes the inherent limitations of conventional PDT by leveraging ambient light for activation and providing a cost-effective, non-invasive, and patient-friendly platform for diabetic wound care, thereby expanding the clinical utility of photodynamic interventions for managing chronic and complex wounds.