Reprogramming Photodynamic Therapy with BODIPY Photosensitizers: From Local Phototoxicity Toward Precision Photodynamic Oncology.

Photodynamic therapy (PDT) offers spatially confined, repeatable and mechanistically orthogonal tumor control, yet its broader clinical impact remains limited by inadequate light access, oxygen dependence and incomplete biological selectivity. Boron-dipyrromethene (BODIPY) dyes provide an unusually programmable platform for addressing these constraints. Although native BODIPYs are fluorescence-biased and inefficient triplet photosensitizers, their absorption, intersystem crossing, reactive oxygen species identity, aggregation, targeting and activation can be independently engineered through modular scaffold modification. In this Review, we present BODIPY as a programmable photochemical chassis for precision-oriented PDT. We first define the structure-photophysics-function relationships that convert BODIPY fluorophores into red- or near-infrared-responsive, type I- or type II-tunable and formulation-compatible photosensitizers. We then introduce a tumor-context-adaptive framework that integrates light-delivery routes, oxygen economy, multiscale targeting, organelle vulnerability and microenvironment-locked activation. Finally, we examine how BODIPY PDT can extend beyond direct cytotoxicity to vascular remodeling, immunogenic cell death, the potential to support in situ vaccination and rational combination therapy, while proposing translational go/no-go criteria for clinically credible candidates. We argue that progress will depend less on molecular complexity than on indication-first co-design of BODIPY chemistry, tumor biology and deployable light hardware.