Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption.

Abstract

We have previously demonstrated that endothelial targeting of gold nanoparticles followed by external beam irradiation can cause specific tumor vascular disruption in mouse models of cancer. The induced vascular damage may lead to changes in tumor physiology, including tumor hypoxia, thereby compromising future therapeutic interventions. In this study, we investigate the dynamic changes in tumor hypoxia mediated by targeted gold nanoparticles and clinical radiation therapy (RT). By using noninvasive whole-body fluorescence imaging, tumor hypoxia was measured at baseline, on day 2 and day 13, post-tumor vascular disruption. A 2.5-fold increase (P<0.05) in tumor hypoxia was measured two days after combined therapy, resolving by day 13. In addition, the combination of vascular-targeted gold nanoparticles and radiation therapy resulted in a significant (P<0.05) suppression of tumor growth. This is the first study to demonstrate the tumor hypoxic physiological response and recovery after delivery of vascular-targeted gold nanoparticles followed by clinical radiation therapy in a human non-small cell lung cancer athymic Foxn1nu mouse model.

• Authors: Needa A Virani, Olivia J Kelada, Sijumon Kunjachan, Alexandre Detappe, Jihun Kwon, Jennifer Hayashi, Ana Vazquez-Pagan, Douglas E Biancur, Thomas Ireland, Rajiv Kumar, Srinivas Sridhar, G Mike Makrigiorgos, Ross I Berbeco
• Journal: PloS one (PLoS One) Vol. 15 Issue 7 Pg. e0236245 ( 2020) ISSN: 1932-6203 [Electronic] United States
• PMID: 32706818 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Gold

Topics

• A549 Cells
• Animals
• Carcinoma, Non-Small-Cell Lung (blood supply, drug therapy, radiotherapy)
• Gold (therapeutic use)
• Humans
• Lung Neoplasms (blood supply, drug therapy, radiotherapy)
• Metal Nanoparticles (therapeutic use)
• Mice
• Mice, Nude
• Optical Imaging (methods)
• Tumor Hypoxia (drug effects, radiation effects)
• Xenograft Model Antitumor Assays