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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.

SUBMITTER: Nukolova NV 

PROVIDER: S-EPMC3809768 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

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