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Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis

Paper ID Volume ID Publish Year Pages File Format Full-Text
6432 490 2013 7 PDF Available
Title
Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis
Abstract

Chemically modified antisense RNA oligonucleotides (antagomir) offer promise for cancer therapies but suffer from poor therapeutic effect after systemic administration. Chemical modification or loading in degradable hydrogels can offer improvements in the accuracy and efficacy for sustained delivery at specific sites. In our approach, antagomir were entrapped with degradable poly(ethylene glycol) (PEG)-based hydrogels, with and without incorporation of imidazole. Superparamagnetic iron oxide nanoparticles (SPION) were simultaneously loaded with intent for magnetic resonance imaging (MRI). The incorporation of imidazole into the PEG hydrogels led to a tunable-pH-response that dictated hydrogel swelling ratio and release rate of antagomir and SPION. As a result, the PEG–imidazole hydrogel swelling ratio and degradation over a 5 week period changed up to 734% and 149% as the pH dropped from 7.4 to 6.7, respectively. The swelling ratio of PEG–imidazole hydrogels was completely reversible over repeatable cycles of pH change. The stimuli-responsive behavior of PEG–imidazole hydrogels was used for the release of antagomir and SPION under conditions consistent with tumor acidosis. This manuscript demonstrates feasibility in designing tunable-pH-responsive hydrogels for loading multimodality therapeutic and contrast agents to enhance the bioactivity of chemically modified antisense RNA oligonucleotide and SPION for acidosis-related tumor therapy and MRI imaging applications.

Keywords
Chemically modified oligonucleotide; Antisense RNA; Superparamagnetic iron oxide nanoparticles; pH-Sensitive; Degradable hydrogel
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Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 17, June 2013, Pages 4387–4393
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us