Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12722-7. doi: 10.1073/pnas.1413027111. Epub 2014 Aug 19.

Refilling drug delivery depots through the blood.

Author information

1
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
2
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Biomedical Engineering, University of California, Davis, CA 95616; and.
3
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115;
5
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
6
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; mooneyd@seas.harvard.edu.

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 blood-borne drug payloads could be modified 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.

KEYWORDS:

DNA nanotechnology; biomaterials; controlled release; nanoparticle; targeting

Comment in

PMID:
25139997
PMCID:
PMC4156738
DOI:
10.1073/pnas.1413027111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center