Localized increase of tissue oxygen tension by magnetic targeted drug delivery

Celine Liong, Daniel Ortiz, Eilleen Ao-Ieong, Mahantesh S. Navati, Joel M. Friedman, Pedro Cabrales

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy- methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O 2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to increase O2 in tumors, enhancing the efficacy of radiation therapies.

Original languageEnglish (US)
Article number265102
JournalNanotechnology
Volume25
Issue number26
DOIs
StatePublished - Jul 4 2014

Fingerprint

Hemoglobin
Tissue
Oxygen
Hemoglobins
Blood
Magnetic fields
Oxygenation
Radiotherapy
L 35
Tumors
Targeted drug delivery
Nanoparticles
Gadolinium
Blood pressure
Animals
Cells
Oxides
Acids

Keywords

  • hemoglobin
  • microcirculation
  • oxygen delivery
  • paramagnets
  • tissue oxygen

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Electrical and Electronic Engineering
  • Mechanical Engineering
  • Mechanics of Materials
  • Materials Science(all)

Cite this

Localized increase of tissue oxygen tension by magnetic targeted drug delivery. / Liong, Celine; Ortiz, Daniel; Ao-Ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro.

In: Nanotechnology, Vol. 25, No. 26, 265102, 04.07.2014.

Research output: Contribution to journalArticle

Liong, Celine ; Ortiz, Daniel ; Ao-Ieong, Eilleen ; Navati, Mahantesh S. ; Friedman, Joel M. ; Cabrales, Pedro. / Localized increase of tissue oxygen tension by magnetic targeted drug delivery. In: Nanotechnology. 2014 ; Vol. 25, No. 26.
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