LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer

Natalia V. Nukolova, Hardeep S. Oberoi, Yi Zhao, Vladimir P. Chekhonin, Alexander V. Kabanov, Tatiana K Bronich

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3913-3921
Number of pages9
JournalMolecular Pharmaceutics
Volume10
Issue number10
DOIs
StatePublished - Oct 7 2013

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Keywords

  • Cisplatin
  • LHRH-targeting
  • Nanogels
  • Ovarian cancer
  • Targeted drug delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Nukolova, N. V., Oberoi, H. S., Zhao, Y., Chekhonin, V. P., Kabanov, A. V., & Bronich, T. K. (2013). LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer. Molecular Pharmaceutics, 10(10), 3913-3921. https://doi.org/10.1021/mp4003688