title: LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer.
abstract: Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35%) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.
authors: Department of Chemistry, Lomonosov Moscow State University , Leninskie Gory, Moscow, 119992, Russia.
authors: Natalia V
authors: NV
authors: Nukolova
authors: Hardeep S
authors: HS
authors: Oberoi
authors: Yi
authors: Y
authors: Zhao
authors: Vladimir P
authors: VP
authors: Chekhonin
authors: Alexander V
authors: AV
authors: Kabanov
authors: Tatiana K
authors: TK
authors: Bronich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008819:Mice, Nude; D018613:Microscopy, Confocal; D000080385:Nanogels; D053758:Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002945:Cisplatin
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