(557a) Photosensitizer Pc 4 Delivery Using EGFR-Targeted Polymeric Micelles for Targeted Photodynamic Therapy of Cancer

Photodynamic Therapy (PDT) is a promising modality for cancer treatment where photoactivation of a photosensitizer (PS) results in energy transfer to molecular oxygen, leading to formation of highly reactive singlet oxygen species, that can induce cell-killing. Formulation and targeted delivery of such photosensitizers to cancer cells, without causing systemic toxicity and non-specific uptake, can increase the therapeutic efficacy of PDT. To this end, we are investigating the formulation and delivery of the PS Pc 4 using amphiphilic block-copolymer-based micelles, surface-decorated with antibodies towards epidermal growth factor receptors (anti-EGFR) for active targeting to EGFR-overexpressing cancer cells. Anti-EGFR conjugated PEG-PCL was synthesized by reacting biocompatible NHS-terminated poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) copolymer with mouse monoclonal anti-EGFR antibody. Antibody conjugation to the block copolymer was studied using a bicinchoninic acid (BCA) protein assay and a dot blot assay. The antibody-conjugated polymer was subsequently used to form micelles at concentrations above CMC in aqueous medium. And the micelles were characterized by NMR and dynamic light scattering. Pc 4 was encapsulated in the hydrophobic core of the micelles and the encapsulation efficiency was estimated by fluorescence and UV spectroscopy. Active cell targeting and PDT studies were done in vitro using an SCC-15 human squamous cell carcinoma cell line which is known to overexpress EGFR. Micelles with Pc 4 but no antibody modification, and micelles with antibody modification but no Pc 4 were used as controls. Our results show that micelle-mediated targeted delivery and photoactivation of Pc 4 lead to enhanced cell killing compared to the controls. Hence our cell-targeted micelle formulation of Pc 4 has considerable promise towards developing site-selective PDT strategies for EGFR-overexpressing cancers.