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: Natalia V Nukolova, Hardeep S Oberoi, Yi Zhao, Vladimir P Chekhonin, Alexander V Kabanov, Tatiana K Bronich
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 10 Issue 10 Pg. 3913-21 (Oct 07 2013) ISSN: 1543-8392 [Electronic] United States
• PMID: 23957812 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Nanogels
• polyethylene glycol polyethyleneimine nanogel
• Polyethylene Glycols
• Polyethyleneimine
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, therapeutic use)
• Cell Line, Tumor
• Cisplatin (administration & dosage, chemistry, therapeutic use)
• Drug Delivery Systems (methods)
• Female
• Flow Cytometry
• Humans
• Mice, Nude
• Microscopy, Confocal
• Nanogels
• Nanoparticles (chemistry)
• Ovarian Neoplasms (drug therapy)
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (chemistry)