title: In vivo and in vitro anti-cancer activities and enhanced cellular uptakes of EGF fragment decorated doxorubicin nano-aggregates.
abstract: Doxorubicin nano-aggregate was prepared for the purpose of epidermal growth factor receptor targeted anti-cancer therapy. An epidermal growth factor fragment composed of 11 amino acids was conjugated to an amino terminal of bi-functional poly(ethylene glycol) and doxorubicin was subsequently conjugated to the other carboxyl terminal of the conjugate. A mixture of the conjugate, free doxorubicin, and triethylamine spontaneously formed nano-sized aggregates in aqueous phase, which was confirmed by transmission electron microscopy and dynamic light scattering. A549 cells incubated with doxorubicin nano-aggregates with the epidermal growth factor fragment showed increased endocytic uptakes of the aggregates compared to unmodified aggregates. Pre-blocking of the epidermal growth factor receptor on the cell significantly decreased a degree of the cellular uptakes. Cytotoxicity of the nano-aggregates was significantly increased when epidermal growth factor fragments were decorated on the surface of doxorubicin nano-aggregates, which was confirmed by a live/dead cell assay and a MTT-based cytotoxicity assay. When doxorubicin nano-aggregates were administered to model animals bearing human lung carcinoma, the epidermal growth factor fragment significantly strengthened in vivo anti-cancer effects of doxorubicin nano-aggregates compared to native doxorubicin or unmodified nano-aggregates. Thus, doxorubicin nano-aggregates decorated with an epidermal growth factor fragment is expected to be a potent anti-cancer agent aiming to tumor tissue over-expressing epidermal growth factor receptors.
authors.affiliation: Department of Biomaterials Engineering, School of Bioscience and Bioengineering, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Shinyoung
authors.initials: S
authors.lastname: Park
authors.forename: Hyuk Sang
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D000903:Antibiotics, Antineoplastic; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D004317:Doxorubicin