From challenges to solutions: insights into AIEgen-based diagnostic and therapeutic strategies for breast cancer

Breast cancer is a malignant neoplasm with high and rising incidence, posing a significant threat and challenge to women's and overall human health. Current mainstream clinical diagnosis and treatment methods still have certain limitations when dealing with complex situations. These limitations include insufficient accuracy in early cancer detection, drug resistance, long-term risks of recurrence and metastasis, and variable therapeutic effects caused by tumor heterogeneity. Compared with traditional organic optical materials, aggregation-induced emission luminogens (AIEgens) possess favorable photophysical properties such as high fluorescence brightness and excellent photobleaching resistance. Through different excited-state energy dissipation pathways, AIEgens can act as imaging contrast agents, photosensitizers (PSs) and photothermal reagents. Further functionalization enhances tumor targeting, reduces off-target toxicity to normal tissues, and enables synergistic tumor cell elimination. AIEgen-based nanomaterials exhibit great potential in high-resolution imaging, phototherapy and synergistic multimodal therapy. They are expected to break through the existing limitations in clinical breast cancer theranostics, and to be promising next-generation nanoplatforms for precise diagnosis and therapy of breast cancer. This review systematically summarizes recent advances in the development of novel AIEgens. We discuss the wavelength-dependent molecular design of AIEgens, the construction and functionalization strategies of AIEgen-based nanomaterials, together with representative applications. Nevertheless, substantial barriers must be resolved before these platforms can reach patients, including Good Manufacturing Practice (GMP)-compliant manufacturing, long-term toxicity and immunogenicity, standardized pharmacokinetic and light-dosimetric evaluation, the limited translatability of rodent optical-penetration data to human breast tissue, and still-evolving regulatory pathways. Accordingly, this review critically analyzes these translation barriers and outlines a forward-looking roadmap for the molecular design, bioengineering, and clinical validation needed to advance AIEgen-based nanomaterials toward precise breast cancer theranostics.