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Article: High-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model

TitleHigh-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model
Authors
KeywordsCancer
Intravital microscopy
Nanoparticles
Serial imaging
Single-walled carbon nanotubes
Specificity
Targeting
Issue Date2013
Citation
Nano Today, 2013, v. 8, n. 2, p. 126-137 How to Cite?
AbstractNanoparticles are under active investigation for the detection and treatment of cancer. Yet our understanding of nanoparticle delivery to tumors is limited by our ability to observe the uptake process on its own scale in living subjects. We chose to study single-walled carbon nanotubes (SWNTs) because they exhibit among the highest levels of tumor uptake across the wide variety of available nanoparticles. We target them using RGD (arginine-glycine-aspartic acid) peptide which directs them to integrins overexpressed on tumor vasculature and on the surface of some tumor cells (e.g., U87MG as used here). We employ intravital microscopy (IVM) to quantitatively examine the spatiotemporal framework of targeted SWNT uptake in a murine tumor model. IVM provided a dynamic microscale window into nanoparticle circulation, binding to tumor blood vessels, extravasation, binding to tumor cells, and tumor retention. RGD-SWNTs bound to tumor vasculature significantly more than controls (P < 0.0001). RGD-SWNTs extravasated similarly compared to control RAD-SWNTs, but post-extravasation we observed as RGD-SWNTs eventually bound to individual tumor cells significantly more than RAD-SWNTs (P < 0.0001) over time. RGD-SWNTs and RAD-SWNTs displayed similar signal in tumor for a week, but over time their curves significantly diverged (P < 0.001) showing increasing RGD-SWNTs relative to untargeted SWNTs. We uncovered the complex spatiotemporal interplay between these competing uptake mechanisms. Specific uptake was delimited to early (1-6 h) and late (1-4 weeks) time-points, while non-specific uptake dominated from 6 h to 1 week. Our analysis revealed critical, quantitative insights into the dynamic, multifaceted mechanisms implicated in ligand-targeted SWNT accumulation in tumor using real-time microscopic observation. © 2013 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/334317
ISSN
2023 Impact Factor: 13.2
2023 SCImago Journal Rankings: 3.483
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSmith, Bryan Ronain-
dc.contributor.authorZavaleta, Cristina-
dc.contributor.authorRosenberg, Jarrett-
dc.contributor.authorTong, Ricky-
dc.contributor.authorRamunas, John-
dc.contributor.authorLiu, Zhuang-
dc.contributor.authorDai, Hongjie-
dc.contributor.authorGambhir, Sanjiv Sam-
dc.date.accessioned2023-10-20T06:47:16Z-
dc.date.available2023-10-20T06:47:16Z-
dc.date.issued2013-
dc.identifier.citationNano Today, 2013, v. 8, n. 2, p. 126-137-
dc.identifier.issn1748-0132-
dc.identifier.urihttp://hdl.handle.net/10722/334317-
dc.description.abstractNanoparticles are under active investigation for the detection and treatment of cancer. Yet our understanding of nanoparticle delivery to tumors is limited by our ability to observe the uptake process on its own scale in living subjects. We chose to study single-walled carbon nanotubes (SWNTs) because they exhibit among the highest levels of tumor uptake across the wide variety of available nanoparticles. We target them using RGD (arginine-glycine-aspartic acid) peptide which directs them to integrins overexpressed on tumor vasculature and on the surface of some tumor cells (e.g., U87MG as used here). We employ intravital microscopy (IVM) to quantitatively examine the spatiotemporal framework of targeted SWNT uptake in a murine tumor model. IVM provided a dynamic microscale window into nanoparticle circulation, binding to tumor blood vessels, extravasation, binding to tumor cells, and tumor retention. RGD-SWNTs bound to tumor vasculature significantly more than controls (P < 0.0001). RGD-SWNTs extravasated similarly compared to control RAD-SWNTs, but post-extravasation we observed as RGD-SWNTs eventually bound to individual tumor cells significantly more than RAD-SWNTs (P < 0.0001) over time. RGD-SWNTs and RAD-SWNTs displayed similar signal in tumor for a week, but over time their curves significantly diverged (P < 0.001) showing increasing RGD-SWNTs relative to untargeted SWNTs. We uncovered the complex spatiotemporal interplay between these competing uptake mechanisms. Specific uptake was delimited to early (1-6 h) and late (1-4 weeks) time-points, while non-specific uptake dominated from 6 h to 1 week. Our analysis revealed critical, quantitative insights into the dynamic, multifaceted mechanisms implicated in ligand-targeted SWNT accumulation in tumor using real-time microscopic observation. © 2013 Elsevier Ltd.-
dc.languageeng-
dc.relation.ispartofNano Today-
dc.subjectCancer-
dc.subjectIntravital microscopy-
dc.subjectNanoparticles-
dc.subjectSerial imaging-
dc.subjectSingle-walled carbon nanotubes-
dc.subjectSpecificity-
dc.subjectTargeting-
dc.titleHigh-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.nantod.2013.02.004-
dc.identifier.scopuseid_2-s2.0-84876910620-
dc.identifier.volume8-
dc.identifier.issue2-
dc.identifier.spage126-
dc.identifier.epage137-
dc.identifier.eissn1878-044X-
dc.identifier.isiWOS:000319236400006-

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