Polymeric-lipid hybrid liposomes co-loaded with curcumin and silver nanoparticles: A strategy for photodynamic therapy in skin cancer.

Skin cancer has seen a rising incidence over the years. Plant-based therapies have been historically widespread, yet the therapeutic efficacy of isolated active compounds often remains limited. Curcumin (CUR), a natural polyphenol with anticancer properties, suffers from low bioavailability, which has been improved through customized formulations and delivery systems like polymeric nanoparticles and liposomes. CUR also acts as an effective photosensitizer (PS) in Photodynamic Therapy (PDT), generating cytotoxic species such as singlet oxygen (O) upon light activation. The combination of CUR with silver nanoparticles (AgNPs) is promising due to the metal-enhanced singlet oxygen generation (MEO) effect. In this context, the present study incorporates CUR and AgNPs into polymeric-lipid hybrid liposomes composed of DPPC and the triblock copolymer F127. The resulting DPPC-F127-AgNPs-CUR vesicles were characterized by diameters lower than 130 nm, low polydispersity (Đ <0.20), zeta potential between ±10 mV, and high encapsulation efficiency (>99%). Spectroscopic analysis confirmed AgNPs incorporation into the liposomes. Photophysical analysis showed a decrease in CUR fluorescence quantum yield, favoring PDT, and high singlet oxygen generation with a strong MEO effect. Ex vivo permeation experiments demonstrated increased CUR retention in the skin layers when delivered via liposomes. Experiments in B16-F10 melanoma cells indicated a cytotoxic effect of CUR-containing formulations, particularly those with CUR and AgNPs exposed to PDT. In vivo studies in mice bearing subcutaneous B16-F10 melanoma showed that intratumoral DPPC-F127-AgNPs-CUR decreased tumor growth and extended survival when administered in combination with PDT.