NIR-activated multifunctional agents for the combined application in cancer imaging and therapy

Anticancer therapies that combine both diagnostic and therapeutic capabilities hold significant promise for enhancing treatment efficacy and patient outcomes. Among these, agents responsive to near-infrared (NIR) photons are of particular interest due to their negligible toxicity and multifunctionality. These compounds are not only effective in photodynamic therapy (PDT), but also serve as contrast agents in various imaging modalities, including fluorescence and photoacoustic imaging. In this review, we explore the photophysical and photochemical properties of NIR-activated porphyrin, cyanine, and phthalocyanines derivatives as well as aggregation-induced emission compounds, highlighting their application in synergistic detection, diagnosis, and therapy. Special attention is given to the design and optimization of these agents to achieve high photostability, efficient NIR absorption, and significant yields of fluorescence, heat, or reactive oxygen species (ROS) generation depending on the application. Additionally, we discuss the incorporation of these compounds into nanocarriers to enhance their solubility, stability, and target specificity. Such nanoparticle-based systems exhibit improved pharmacokinetics and pharmacodynamics, facilitating more effective tumor targeting and broadening the application range to photoacoustic imaging and photothermal therapy. Furthermore, we summarize the application of these NIR-responsive agents in multimodal imaging techniques, which combine the advantages of fluorescence and photoacoustic imaging to provide comprehensive diagnostic information. Finally, we address the current challenges and limitations of photodiagnosis and phototherapy and highlight some critical barriers to their clinical implementation. These include issues related to their phototoxicity, limited tissue penetration, and potential off-target effects. The review concludes by highlighting future research directions aimed at overcoming these obstacles, with a focus on the development of next-generation agents and platforms that offer enhanced therapeutic efficacy and imaging capabilities in the field of cancer treatment.