Work

Ultrasound-activated Agents Comprised of 5FU-bearing Nanoparticles Bonded to Microbubbles Inhibit Solid Tumor Growth and Improve Survival

Year: 2013

Type: article

Abstract: Nanoparticle (NP) drug delivery vehicles may eventually offer improved tumor treatments; however, NP delivery from the bloodstream to tumors can be hindered by poor convective and/or diffusive transport. We tested whether poly(lactic-co-glycolic acid) NP delivery can be improved by covalently linking them to ultrasound (US)-activated microbubbles in a "composite-agent" formulation and whether drug 5-fluorouracil (5FU)-loaded NPs delivered in this fashion inhibit the growth of tumors that are typically not responsive to intravenously administered 5FU. After intravenous composite-agent injection, C6 gliomas implanted on Rag-1(-/-) mice were exposed to pulsed 1 MHz US, resulting in the delivery of 16% of the initial NP dose per gram tissue. This represented a five- to 57-fold increase in NP delivery when compared to multiple control groups. 5FU-bearing NP delivery from the composite-agent formulation resulted in a 67% reduction in tumor volume at 7 days after treatment, and animal survival increased significantly when compared to intravenous soluble 5FU administration. We conclude that NP delivery from US-activated composite agents may improve tumor treatment by offering a combination of better targeting, enhanced payload delivery, and controlled local drug release.

Source: Molecular Therapy

DOI: 10.1038/mt.2013.259

Authors: Caitlin W Burke, Eben Alexander, Kelsie Timbie, Alexander L Kilbanov, Richard J Price

Institutions: University of Virginia Health System, University of Virginia

Language: English

Topic: Ultrasound and Hyperthermia Applications

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500