Abstract: Remediation of Radiation Associated Vasculopathy Utilizing a Novel Angiogenic Nanotechnology
Year: 2017
Type: conference-abstract
Abstract: INTRODUCTION: Although radiotherapy is often necessary in oncologic management, it inhibits angiogenesis leading to devastating consequences in adjacent healthy tissues and subsequent tissue healing. Deferoxamine (DFO) has been demonstrated to bolster angiogenesis following radiotherapy, making it an attractive therapeutic to reconstructive surgeons treating oncologic patients. In current formulation, DFO would require frequent clinic visits for painful localized injections rendering it suboptimal for clinical use. This prompted us to develop an implantable nanoparticle formulation of DFO. We posit that the administration of nano-DFO will remediate an in vitroradiotherapeutic model of angiogenesis comparable to the levels achieved with standard DFO. Establishing equivalency of nano-DFO would offer promise for oncologic patients requiring both radiotherapy and reconstruction by providing a more clinically translatable single implantable dose of DFO. METHODS: Three groups of irradiated (5Gy) endothelial cells (n=4/group) were treated with 50µM DFO, 50µM nano-DFO, or 100µM nano-DFO. All cultures were video recorded simultaneously with live cell imaging at 150x magnification over four hours. Hourly tubule counts, a measure of vascular architecture, was measured for each experimental group with comparison using ANOVA with p<0.05 considered statistically significant. RESULTS: We observed no statistical differences in angiogenic ability between normal DFO and nano-DFO for any doses through 3 hours. There were, however, trending increases between 50µM DFO and 100µM nano-DFO at 2 and 3 hours (p= 0.055 and 0.066). Furthermore, we observed a statistical increase in vascular networks between 50µM DFO and 100µM nano-DFO at 4 hours (p= 0.033). Within two hours of incubation, 100µM nano-DFO cultures achieved more robust vascular architecture in comparison to the normal DFO experimental group. CONCLUSION: Our data establishes in vitro angiogenic efficacy and translational dosing for a novel nano-DFO in a comparative analysis with the clinically cumbersome standard formulation of DFO. This study provides identification of a nano-technology with a promising capacity to prevent radiation-induced tissue injury through enhanced angiogenesis with in an improved method of delivery for facilitation of early clinical adoption.
Authors: Alicia Elizabeth Snider, Alexis Donneys, Kavitha Ranganathan, Noah S. Nelson, Jose J. Rodriguez, Russell E. Ettinger, Laird Forrest, Mark S. Cohen, Steven R. Buchman
Institution: University of Michigan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W2758831215