Perylene Diimide Derivatives: From Molecular Engineering to Precision Cancer Theranostics

Perylene diimide (PDI) derivatives are a class of well-established organic optoelectronic materials with a rigid π-conjugated fused ring framework, which have been extensively explored for biomedical applications including fluorescence imaging, photoacoustic imaging, and tumor phototherapy over the past decades. Benefiting from their intrinsic merits, including high fluorescence quantum yield (FQY), tunable photophysical properties, excellent photochemical stability, and facile structural functionalization, PDIs have shown outstanding performance in photodynamic therapy (PDT) and photothermal therapy (PTT). However, the biomedical translation of PDIs still faces critical bottlenecks: insufficient water solubility and severe aggregation-caused quenching (ACQ) effect derived from strong intermolecular π–π stacking, limited tissue penetration depth from short-wavelength absorption/emission, tumor microenvironment hypoxia that restricts type II PDT efficacy, and unsatisfactory photothermal conversion efficiency (PCE) of conventional PDI derivatives for PTT. This review systematically summarizes the research progress of PDIs in biomedical fields, focusing on molecular design strategies for spectral redshift, water solubility enhancement, and phototherapeutic performance optimization. Meanwhile, the structure–property relationships of PDI derivatives are elaborated in depth from the perspective of molecular orbital engineering and aggregation state regulation. Finally, existing challenges and future development directions in biomedical translation are discussed to provide guidance for the rational design of high-performance PDI-based diagnostic and therapeutic agents.