Multimodal in vivo imaging exposes the voyage of nanoparticles in tumor microcirculation

Randall Toy, Elliott Hayden, Andrew Camann, Zachary Berman, Peter Vicente, Emily Tran, Joseph Meyers, Jenna Pansky, Pubudu M. Peiris, Hanping Wu, Agata Exner, David Wilson, Ketan B. Ghaghada, Efstathios Karathanasis

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Tumors present numerous biobarriers to the successful delivery of nanoparticles. Decreased blood flow and high interstitial pressure in tumors dictate the degree of resistance to extravasation of nanoparticles. To understand how a nanoparticle can overcome these biobarriers, we developed a multimodal in vivo imaging methodology, which enabled the noninvasive measurement of microvascular parameters and deposition of nanoparticles at the microscopic scale. To monitor the spatiotemporal progression of tumor vasculature and its vascular permeability to nanoparticles at the microcapillary level, we developed a quantitative in vivo imaging method using an iodinated liposomal contrast agent and a micro-CT. Following perfusion CT for quantitative assessment of blood flow, small animal fluorescence molecular tomography was used to image the in vivo fate of cocktails containing liposomes of different sizes labeled with different NIR fluorophores. The animal studies showed that the deposition of liposomes depended on local blood flow. Considering tumor regions of different blood flow, the deposition of liposomes followed a size-dependent pattern. In general, the larger liposomes effectively extravasated in fast flow regions, while smaller liposomes performed better in slow flow regions. We also evaluated whether the tumor retention of nanoparticles is dictated by targeting them to a receptor overexpressed by the cancer cells. Targeting of 100 nm liposomes showed no benefits at any flow rate. However, active targeting of 30 nm liposomes substantially increased their deposition in slow flow tumor regions (∼12-fold increase), which suggested that targeting prevented the washout of the smaller nanoparticles from the tumor interstitium back to blood circulation.

Original languageEnglish (US)
Pages (from-to)3118-3129
Number of pages12
JournalACS Nano
Volume7
Issue number4
DOIs
StatePublished - Apr 23 2013
Externally publishedYes

Keywords

  • angiogenesis
  • angiogram
  • blood flow
  • high-resolution imaging
  • nanoparticle contrast agent
  • nanoparticle extravasation
  • transport of nanoparticles
  • vascular permeability

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Multimodal in vivo imaging exposes the voyage of nanoparticles in tumor microcirculation'. Together they form a unique fingerprint.

  • Cite this

    Toy, R., Hayden, E., Camann, A., Berman, Z., Vicente, P., Tran, E., Meyers, J., Pansky, J., Peiris, P. M., Wu, H., Exner, A., Wilson, D., Ghaghada, K. B., & Karathanasis, E. (2013). Multimodal in vivo imaging exposes the voyage of nanoparticles in tumor microcirculation. ACS Nano, 7(4), 3118-3129. https://doi.org/10.1021/nn3053439