title: Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and Activation of Photodynamic Therapy Drug in Glioblastomas.
abstract: Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. AuNPs conjugated with peptides against both the epidermal growth factor and transferrin receptors and loaded with the photosensitizer phthalocyanine 4 (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ∼41 nm improved both specificity and worked synergistically to decrease time of maximal accumulation in human glioma cells that overexpressed two cell surface receptors as compared to cells that overexpressed only one. Enhanced cellular association and increased cytotoxicity were achieved. In vivo studies show notable accumulation of these agents in the brain tumor regions.
authors.forename: Suraj
authors.initials: S
authors.lastname: Dixit
authors.forename: Kayla
authors.initials: K
authors.lastname: Miller
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Emilie
authors.initials: E
authors.lastname: McKinnon
authors.forename: Thomas
authors.initials: T
authors.lastname: Novak
authors.affiliation: Department of Chemistry, Case Western Reserve University , Cleveland, Ohio 44106, United States.
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Kenney
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Broome
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005909:Glioblastoma / Q000188:drug therapy*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors*; D000068936:Theranostic Nanomedicine; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D007211:Indoles; D010446:Peptide Fragments; D017319:Photosensitizing Agents; D011990:Receptors, Transferrin; C107448:phthalocyanine Pc 4; D006046:Gold; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Pc 4; epidermal growth factor; glioblastoma; gold nanoparticles; transferrin