A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer

Targeted photodynamic therapy (TPDT) involves the administration of a photosensitizer (PS) conjugated with a targeting moiety followed by light activation. The systemic toxicity associated with conventional therapy may thus be significantly reduced in TPDT due to the dual selectivity provided by the spatial localization of the illumination as well as the target-localizing ability of the conjugate. Herein, a photo-immuno-conjugate-associating-liposome (PICAL) for TPDT has been developed in which the FDA approved benzoporphyrin derivative monoacid A (BPD) and the Cetuximab antibody for epidermal growth factor receptor (EGFR) were associated into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. Results have shown that the BPD molecules adsorbed into PICAL have stable optical behavior and a higher fluorescence quantum yield than free-BPD. The Cetuximab adsorbed into PPL selectively binds to cells that overexpress EGFR. The inhibition of EGFR signaling by PICAL has enhanced PDT-mediated ovarian cancer cell death.From the Clinical EditorIn this basic science study, a photo-immuno-conjugate-associating-liposome for targeted photodynamic therapy is investigated. The FDA-approved benzoporphyrin derivative monoacid A and an epidermal growth factor receptor antibody were assembed into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. The authors demonstrate therapeutic efficacy of the above construct in an ovarian tumor system.

Photoimmunotargeting is a useful dual strategy for the selective destruction of cancer cells that over expressed EGFR and also exerts the receptor-blocking biological function of C225. The figure shows an envisioned schema of PICAL and tumor cells showing the proposed mechanism of PICAL that targets EGF receptors. The FDA approved BPD photosensitiser and Cetuximab monoclonal antibody were physically attached to a stable preformed liposome.Figure optionsDownload high-quality image (222 K)Download as PowerPoint slide