Biocompatible Nanoparticles Encapsulation of Fluorenyl-Porphyrins: Impact of Arm Structural Modifications on Two-Photon Phototherapeutic Performance.

In this work, we explore the use of porphyrin/fluorene assemblies as luminescent photosensitizers (PSs) for two-photon photodynamic therapy in biological media. In this context, we systematically investigated a series of star-shaped hydrophobic porphyrins bearing four arms composed of either a single fluorenyl unit or two fluorenyls linked by triple or double bonds. These fluorenyl-porphyrins, previously identified as efficient fluorescent two-photon PSs in organic solvents, were encapsulated at various loadings in poly(benzyl malate)-based polymeric nanoparticles (NPs). Notably, promising PDT activity was observed in aqueous media for formulations with high PS loading (25 wt %), confirming this encapsulation strategy as an accessible and cost-effective approach for porphyrin biocompatibilization. Despite their strong confinement within the nanoparticles, the encapsulated porphyrins retained significant luminescent properties suitable for bioimaging, supporting the theranostic potential of these nanosystems.