Targeted photodynamic-induced singlet oxygen production by peptide-conjugated biodegradable nanoparticles for treatment of skin melanoma

Abstract Background Photodynamic therapy (PDT) has been determined to be a promising treatment modality in the most resistant tumors such as malignant melanoma. However, the key cytotoxic agent of PDT, -singlet oxygen ( 1 O 2 ) - represents a high risk of photodynamic-associated side effects e.g. skin photosensitization. Recently, controllable photosensitization, where 1 O 2 is produced on demand, has received increasing attention. In our study, this could be achieved via loading the photosensitizer (PS) in nanoparticles (NPs) decorated with target-specific moieties characterized by 1 O 2 quenching abilities to specifically locate the PS in the targeted cells and assure that 1 O 2 is only produced where desired after cellular processing. Methods Polymeric and hybrid lipid-polymer NPs were formulated and assayed for their physicochemical properties. This was followed by conjugation with an active targeting ligand, cRGDyk, cyclic (Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine) peptide. Finally, photodynamic potential of the selected formulations was assayed by quantification of 1 O 2 production and in vitro cytotoxicity. Results Three formulations were selected and nominated to be formulations of choice ( FOCs ); FOC-1 (200 nm, polymeric), FOC-2 (130 nm, polymeric) and FOC-3 (200 nm, hybrid). Physicochemical properties, most importantly particle size and NPs’ composition have shown to be the major determinants in targeted NPs’ 1 O 2 production and PDT-mediated cytotoxicity of melanoma. Conclusion Proper selection of formulations intended for PDT application and target-specific ligands could achieve dual targeting; enhanced accumulation of NPs and protection of 1 O 2 production elsewhere other than target cells.