Porphyrin-Based Bioconjugates for Image-Guided Photodynamic Therapy: Synthetic Strategies

Abstract Porphyrin-based conjugated systems that integrate photodynamic therapy and bioimaging functions into a single molecular platform have garnered significant attention. Their appeal lies in the remarkable versatility of the porphyrin scaffold, which can be readily functionalized to incorporate diverse therapeutic and diagnostic components. Nevertheless, the transition from conceptual potential to experimentally validated multifunctional systems is not always straightforward. Accordingly, this review highlights selected synthetic strategies used in the development of porphyrin conjugates that have been successfully demonstrated for both therapeutic and bioimaging applications. Particular emphasis is given to the selection of conjugation strategies, linker architectures, targeting moieties, and metal coordination approaches as these factors strongly influence not only the synthetic efficiency, yield, structural complexity, and purification but also the physical−chemical features of the porphyrin core, rather than the biological performance. Robust and versatile transformations, solely prepared through covalent linkage, including click reactions, cross-coupling methodologies, amide bond formation, and postfunctionalization strategies, have enabled the construction of increasingly sophisticated conjugates incorporating targeting ligands, hydrophilic fragments, and imaging probes, often without compromising the integrity of the photosensitizing unit. The examples discussed herein illustrate the advantages and limitations associated with different synthetic approaches as well as their impact on key molecular features. By comparing the methodologies currently available, this review provides an overview of the synthetic toolbox for porphyrin conjugation and highlights the relationship between synthetic design, structural properties, and biological performance in porphyrin-based systems developed for both photodynamic and imaging applications.