Refilling drug delivery depots through the blood

Yevgeny Brudno, Eduardo Silva, Cathal J. Kearney, Sarah A. Lewin, Alex Miller, Kathleen D. Martinick, Michael Aizenberg, David J. Mooney

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Local drug delivery depots have significant clinical utility, but there is currently no noninvasive technique to refill these systems once their payload is exhausted. Inspired by the ability of nanotherapeutics to target specific tissues, we hypothesized that bloodborne drug payloads could bemodified to home to and refill hydrogel drug delivery systems. To address this possibility, hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target for drug payloads in the form of free alginate strands carrying complementary ODNs. Coupling ODNs to alginate strands led to specific binding to complementary-ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to a drug payload, sequence-targeted refilling of a delivery depot consisting of intratumor hydrogels completely abrogated tumor growth. These results suggest a new paradigm for nanotherapeutic drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.

Original languageEnglish (US)
Pages (from-to)12722-12727
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number35
DOIs
StatePublished - Sep 2 2014

Keywords

  • Biomaterials
  • Controlled release
  • DNA nanotechnology
  • Nanoparticle
  • Targeting

ASJC Scopus subject areas

  • General

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    Brudno, Y., Silva, E., Kearney, C. J., Lewin, S. A., Miller, A., Martinick, K. D., Aizenberg, M., & Mooney, D. J. (2014). Refilling drug delivery depots through the blood. Proceedings of the National Academy of Sciences of the United States of America, 111(35), 12722-12727. https://doi.org/10.1073/pnas.1413027111