title: VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells.
abstract: Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed by not only core tumor cells but also by migrated glioma cells, which are responsible for resistance and rapid progression of brain tumors. The purpose of the present study was to develop the liposomal drug delivery system combining enhanced loading capacity of cisplatin and high binding affinity to glioma cells. This was achieved by using of highly soluble cisplatin analogue, cis-diamminedinitratoplatinum(II), and antibodies against the native form of VEGF or VEGFR2 conjugated to liposome surface. The developed drug delivery system revealed sustained drug release profile, high affinity to antigens, and increased uptake by glioma C6 and U-87 MG cells. Pharmacokinetic study on glioma C6-bearing rats revealed prolonged blood circulation time of the liposomal formulation. The above features enabled the present drug delivery system to overcome both poor pharmacokinetics typical for platinum formulations and low loading capacity typical for conventional liposomal cisplatin formulations.
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky Medical Research Center of Psychiatry and Narcology , Moscow, Russia.|Department of Molecular and Cellular Biology, The International Biotechnology Center Generium , Volginsky Village, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Shein
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Moscow, Russia.
authors.forename: Ilya I
authors.initials: II
authors.lastname: Kuznetsov
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky Medical Research Center of Psychiatry and Narcology , Moscow, Russia.
authors.forename: Tatiana O
authors.initials: TO
authors.lastname: Abakumova
authors.affiliation: Institute of Macromolecular Compounds, Russian Academy of Sciences , St. Petersburg, Russia.|Institute of Chemistry, St. Petersburg State University , St. Petersburg, Russia.
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Chelushkin
authors.affiliation: Department of Medical Nanobiotechnology, Russian National Research Medical University , named after N.I. Pirogov, Moscow, Russia.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Melnikov
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky Medical Research Center of Psychiatry and Narcology , Moscow, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Korchagina
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Moscow, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Bychkov
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Moscow, Russia.
authors.forename: Irina F
authors.initials: IF
authors.lastname: Seregina
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Moscow, Russia.|Institute for Spectroscopy, Russian Academy of Sciences , Troitsk, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Bolshov
authors.affiliation: Chemistry Department, Lomonosov Moscow State University , Moscow, Russia.|Center for Nanotechnology in Drug Delivery, Molecular Pharmaceutics Division, UNC Eshelman School of Pharmacy , Chapel Hill, North Carolina 27599, United States.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky Medical Research Center of Psychiatry and Narcology , Moscow, Russia.|Department of Medical Nanobiotechnology, Russian National Research Medical University , named after N.I. Pirogov, Moscow, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Chekhonin
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky Medical Research Center of Psychiatry and Narcology , Moscow, Russia.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Nukolova
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D018613:Microscopy, Confocal; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D002945:Cisplatin
keywords: PEGylated liposomes; anti-VEGF and anti-VEGFR2 monoclonal antibody; cisplatin; glioma; targeted drug delivery