BODIPY-based photosensitizers for cancer phototherapy: photophysical modulation, ROS-mediated cell death and phototheranostic applications.

Boron-dipyrromethene (BODIPY)-based systems represent a versatile class of photosensitizers for cancer phototherapy due to their tunable photophysical properties, structural stability and multifunctional adaptability. This review presents an integrated perspective on BODIPY photochemistry at the interface of tumor microenvironment (TME) engineering, regulated cell death (RCD), and cancer immunotherapy. Review begins with a summary of the fundamental photophysical principles of light absorption, excited state dynamics, and reactive oxygen species (ROS) generation, which are the basis for rational photosensitizer design, advanced molecular engineering strategies such as the extension of π-conjugation, modulation of intersystem crossing, heavy-atom-free design and subcellular targeting are further highlighted for optimizing photodynamic performance. Particular attention is paid to TME-responsive systems that allow spatiotemporal activation under conditions such as hypoxia, acidity, and redox imbalance, which not only improve therapeutic selectivity but also actively reprogram the tumor microenvironment, further ROS mediated regulated cell death pathways such as apoptosis, ferroptosis and pyroptosis and their integration into immunogenic cell death and systemic immune activation studied. Review also discusses the combination of photodynamic therapy and immunotherapy, including multifunctional platforms that combine ROS generation and immune modulation to improve antitumor efficacy. Moreover, the recent advances of imaging-guided theranostic systems are summarized to show the capabilities of BODIPY-based platforms in real-time monitoring and precision therapy. Finally, current challenges related to oxygen dependence, formulation, biosafety, biodegradability and clinical translation are discussed, together with future directions for the development of adaptive and clinically relevant systems. Overall, this review provides a unifying framework linking BODIPY molecular design with biological and therapeutic outcomes, offering insights into the development of next-generation BODIPY-based phototheranostic platforms.