Targeted Photodynamic-Induced Singlet Oxygen Production by Peptide-Conjugated Biodegradable Nanoparticles for Treatment of Skin Melanoma

Publication date: Available online 7 June 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Aya Ahmed Sebak, Iman Imam Gomaa, Aliaa Nabil ElMeshad, Mahmoud Hashem AbdelKader
BackgroundPhotodynamic therapy (PDT) has been determined to be a promising treatment modality in the most resistant tumors as malignant melanoma. Meanwhile, the key cytotoxic agent of PDT, -singlet oxygen (¹O2) - represents a high risk of photodynamic-associated side effects e.g. skin photosensitization. Recently, controllable photosensitization, where ¹O2 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 ¹O2 quenching abilities to specifically locate the PS in the targeted cells and assure that ¹O2 is only produced where desired after cellular processing.MethodsPolymeric 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 ¹O2 production and in vitro cytotoxicity.ResultsThree 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' ¹O2 production and PDT-mediated cytotoxicity of melanoma.ConclusionProper selection of formulations intended for PDT application and target-specific ligands could achieve dual targeting; enhanced accumulation of NPs and protection of ¹O2 production elsewhere other than target cells.

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