Biodegradable, cationic methacrylamide-based polymers for gene delivery to ovarian cancer cells in mice.

Abstract

A series of cationic, methacrylamide polymers was tested for use as a biodegradable gene carrier in ovarian cancer. Tumor transfection activity of polyplexes consisting of a reporter gene and different methacrylamide polymers was assessed, after intraperitoneal injection in mice bearing an ovarian cancer xenograft. In this model, polyplexes based on poly(HPMA-DMAE) showed transfection activity similar to polyplexes based on the nondegradable and rather toxic polyethylenimine (PEI22). The tumor transfection activity of the pHPMA-DMAE polyplexes was remarkable considering their poor transfection activity in in vitro assays. Polyplexes based on pHPMA-DMAE were devoid of any cytotoxicity and mediated highest transfection activity at the highest N/P ratio investigated. Tumor cell gene expression after a single administration of these polyplexes rapidly declined within time, at a similar rate to that observed after injection with polyplexes based on PEI22. Incubation of the polyplexes with hyaluronic acid (HA), a polyanion accumulating in the ascitic fluid of ovarian cancer bearing mice, changed the physical characteristics of the pHPMA-DMAE and PEI22 polyplexes. The transfection activity of PEI22-based polyplexes, but not that of pHPMA-DMAE based polyplexes, was strongly impaired by HA. Differences in HA sensitivity might have contributed to the in vivo gene expression activities of pHPMA-DMAE- and PEI22-based polyplexes. pHPMA-DMAE-based polyplexes have potential for use in ovarian cancer therapy due to their considerable transfection activity, their low cytotoxicity, and their HA resistance.

• Authors: Holger K de Wolf, Jordy Luten, Cor J Snel, Gert Storm, Wim E Hennink
• Journal: Molecular pharmaceutics (Mol Pharm) 2008 Mar-Apr Vol. 5 Issue 2 Pg. 349-57 ISSN: 1543-8384 [Print] United States
• PMID: 18181574 (Publication Type: Journal Article)

Chemical References

• Methacrylates
• Polymers
• Polyethyleneimine
• Hyaluronic Acid
• 2-(dimethylamino)ethyl methacrylate
• hydroxypropyl methacrylate

Topics

• Animals
• Cell Line, Tumor
• Female
• Gene Transfer Techniques
• Genetic Therapy
• Humans
• Hyaluronic Acid (metabolism)
• Methacrylates (administration & dosage)
• Mice
• Mice, Inbred BALB C
• Ovarian Neoplasms (therapy)
• Polyethyleneimine (administration & dosage)
• Polymers (administration & dosage)
• Transfection