Show simple item record

dc.contributor.authorWong, Cliff
dc.contributor.authorStylianopoulos, Triantafyllos
dc.contributor.authorCui, Jian
dc.contributor.authorMartin, John
dc.contributor.authorChauhan, Vikash
dc.contributor.authorJiang, Wen
dc.contributor.authorPopović, Zoran
dc.contributor.authorJain, Rakesh
dc.contributor.authorBawendi, Moungi
dc.contributor.authorFukumura, Dai
dc.date.accessioned2019-10-13T16:03:06Z
dc.date.issued2011
dc.identifier.citationWong, C., T. Stylianopoulos, J. Cui, J. Martin, V. P. Chauhan, W. Jiang, Z. Popovic, R. K. Jain, M. G. Bawendi, and D. Fukumura. 2011. “Multistage Nanoparticle Delivery System for Deep Penetration into Tumor Tissue.” Proceedings of the National Academy of Sciences 108 (6): 2426–31. doi:10.1073/pnas.1018382108.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41542781*
dc.description.abstractCurrent Food and Drug Administration-approved cancer nanotherapeutics, which passively accumulate around leaky regions of the tumor vasculature because of an enhanced permeation and retention (EPR) effect, have provided only modest survival benefits. This suboptimal outcome is likely due to physiological barriers that hinder delivery of the nanotherapeutics throughout the tumor. Many of these nanotherapeutics are approximate to 100 nm in diameter and exhibit enhanced accumulation around the leaky regions of the tumor vasculature, but their large size hinders penetration into the dense collagen matrix. Therefore, we propose a multistage system in which 100-nm nanoparticles "shrink" to 10-nm nanoparticles after they extravasate from leaky regions of the tumor vasculature and are exposed to the tumor microenvironment. The shrunken nanoparticles can more readily diffuse throughout the tumor's interstitial space. This size change is triggered by proteases that are highly expressed in the tumor microenvironment such as MMP-2, which degrade the cores of 100-nm gelatin nanoparticles, releasing smaller 10-nm nanoparticles from their surface. We used quantum dots (QD) as a model system for the 10-nm particles because their fluorescence can be used to demonstrate the validity of our approach. In vitro MMP-2 activation of the multistage nanoparticles revealed that the size change was efficient and effective in the enhancement of diffusive transport. In vivo circulation half-life and intratumoral diffusion measurements indicate that our multistage nanoparticles exhibited both the long circulation half-life necessary for the EPR effect and the deep tumor penetration required for delivery into the tumor's dense collagen matrix.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleMultistage nanoparticle delivery system for deep penetration into tumor tissue
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorFukumura, Dai::929b7d0391322bd39ce202f783b9a000::600
dc.date.available2019-10-13T16:03:06Z
dash.workflow.comments1Science Serial ID 92071
dc.identifier.doi10.1073/pnas.1018382108
dash.source.volume108;6
dash.source.page2426


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record