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

Ching Wen Lin, S. Ja Tseng, Ivan M. Kempson, Shuenn Chen Yang, Tse Ming Hong, Pan Chyr Yang

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4387-4393
Number of pages7
JournalBiomaterials
Volume34
Issue number17
DOIs
Publication statusPublished - 2013 Jun

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis'. Together they form a unique fingerprint.

Cite this