Development of BODIPY-based photosensitizing nanoparticles for photodynamic therapy of skin cancer

Cutaneous melanoma is poorly responsive to photodynamic therapy (PDT) because melanin absorbs and scatters light, reducing photon availability to the photosensitizer (PS). Thus, PSs absorbing in spectral regions less affected by melanin are needed. Boron-dipyrromethene (BODIPY) derivatives are promising PSs owing to their favorable photophysical properties, but their hydrophobicity may limit topical penetration. Conjugation with phospholipids, such as dioleoylphosphatidylethanolamine (DOPE), may increase their affinity for lipidic structures, while liposomal incorporation may improve dispersion and topical delivery. Thus, this study aimed to develop and characterize BODIPY derivatives and liposomal systems for their future application in melanoma PDT. A novel diiodinated BODIPY derivative was synthesized and conjugated to DOPE (BODIPY-DOPE). Singlet oxygen generation was evaluated using 1,3-diphenylisobenzofuran. Liposomes composed of distearoylphosphatidylcholine, cholesterol, and distearoylphosphatidylethanolamine-polyethylene glycol at a 66:30:4 ratio were prepared by thin-film hydration followed by sonication. The unconjugated BODIPY was incorporated during film formation. Formulations were characterized by hydrodynamic diameter, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and transmission electron microscopy. The BODIPY derivative exhibited a singlet oxygen quantum yield of 0.75±0.14, while BODIPY-DOPE showed 0.54±0.15, indicating that conjugation preserved photodynamic activity. Blank liposomes displayed spherical morphology, a diameter of 135±1 nm, PDI<0.2, and ZP of −19±1 mV. BODIPY encapsulation efficiency exceeded 99% and did not significantly alter the physicochemical characteristics of the liposomes. These results demonstrate the feasibility of incorporating the synthesized BODIPY into stable nanosized liposomes, supporting their potential as a platform for topical melanoma PDT. Further studies will investigate BODIPY-DOPE-loaded liposomes and BODIPY skin penetration from the developed formulations.