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

Molecular Pharmaceutics
Holger K de WolfWim E Hennink

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 pH...Continue Reading

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Citations

Apr 16, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Luís NovoWim E Hennink
Sep 11, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Luís NovoWim E Hennink
Dec 21, 2010·Gynecologic Oncology·Paul S KimReema Zeineldin
Jan 19, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jordy LutenWim E Hennink
Jul 28, 2010·Biotechnology Progress·Eun-Kyung LimSeungjoo Haam
Apr 16, 2009·Tissue Engineering. Part a·Kyung Sook KimMoon Suk Kim
Apr 23, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Friederike RichterAnja Traeger
Oct 18, 2014·Macromolecular Rapid Communications·Lutz NuhnRudolf Zentel
Apr 12, 2019·Drug Delivery and Translational Research·Bo LouWim E Hennink
Nov 6, 2010·Bioconjugate Chemistry·Amir K VarkouhiWim E Hennink

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