Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer

Targeted drug delivery using epidermal growth factor peptide-targeted gold nanoparticles (EGF_pep-Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGF_pep-Au NP-Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGF_pep-Au NP-Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGF_pep-Au NP-Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGF_pep-Au NP-Pc 4 results in interrupted tumor growth when compared with EGF_pep-Au NP control mice when selectively activated with light. These data demonstrate that EGF_pep-Au NP-Pc 4 utilizes cancer-specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery.