Biodegradable, cationic methacrylamide-based polymers for gene delivery to ovarian cancer cells in mice
| Autor: | Cor J. Snel, Jordy Luten, Wim E. Hennink, Holger K. de Wolf, Gert Storm |
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| Rok vydání: | 2008 |
| Předmět: |
Polymers
medicine.medical_treatment Genetic enhancement Intraperitoneal injection Pharmaceutical Science Gene delivery Transfection chemistry.chemical_compound Mice Cell Line Tumor Drug Discovery medicine Methacrylamide Animals Humans Polyethyleneimine Hyaluronic Acid Cytotoxicity Ovarian Neoplasms Reporter gene Polyethylenimine Mice Inbred BALB C Chemistry Gene Transfer Techniques Genetic Therapy Molecular biology Molecular Medicine Methacrylates Female |
| Zdroj: | Molecular pharmaceutics. 5(2) |
| ISSN: | 1543-8384 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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