Show simple item record

dc.contributor.authorWong, C.en
dc.contributor.authorStylianopoulos, T.en
dc.contributor.authorCui, J.en
dc.contributor.authorMartin, J.en
dc.contributor.authorChauhan, V. P.en
dc.contributor.authorJiang, W.en
dc.contributor.authorPopovic, Z.en
dc.contributor.authorJain, R. K.en
dc.contributor.authorBawendi, M. G.en
dc.contributor.authorFukumura, D.en
dc.creatorWong, C.en
dc.creatorStylianopoulos, T.en
dc.creatorCui, J.en
dc.creatorMartin, J.en
dc.creatorChauhan, V. P.en
dc.creatorJiang, W.en
dc.creatorPopovic, Z.en
dc.creatorJain, R. K.en
dc.creatorBawendi, M. G.en
dc.creatorFukumura, D.en
dc.date.accessioned2019-05-06T12:24:50Z
dc.date.available2019-05-06T12:24:50Z
dc.date.issued2011
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/48939
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 ≈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 nano-particles, 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.en
dc.language.isoengen
dc.sourceProceedings of the National Academy of Sciences of the United States of Americaen
dc.subjectarticleen
dc.subjecthumanen
dc.subjectNeoplasmsen
dc.subjectHumansen
dc.subjectcontrolled studyen
dc.subjectpriority journalen
dc.subjecthuman tissueen
dc.subjecttumor microenvironmenten
dc.subjectgelatinase Aen
dc.subjecttumor vascularizationen
dc.subjectdrug half lifeen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectcancer tissueen
dc.subjectin vitro studyen
dc.subjectNeovascularizationen
dc.subjectPathologicen
dc.subjectTumoren
dc.subjectCell Lineen
dc.subjectcollagenen
dc.subjectdrug delivery systemen
dc.subjectDrug Delivery Systemsen
dc.subjectdrug extravasationen
dc.subjectDrug deliveryen
dc.subjectdrug diffusionen
dc.subjectCancer therapyen
dc.subjectnanoparticleen
dc.subjectfluorescenceen
dc.subjectdrug penetrationen
dc.subjectNanomedicineen
dc.subjectnanocarrieren
dc.subjectXenograft Model Antitumor Assaysen
dc.subjectSCIDen
dc.subjectParticle Sizeen
dc.subjectin vivo studyen
dc.subjectgelatinen
dc.subjectquantum doten
dc.subjectdrug accumulationen
dc.subjectenzyme activationen
dc.subjectMatrix Metalloproteinase 2en
dc.subjectQuantum Dotsen
dc.subjectsurface propertyen
dc.titleMultistage nanoparticle delivery system for deep penetration into tumor tissueen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1073/pnas.1018382108
dc.description.volume108
dc.description.startingpage2426
dc.description.endingpage2431
dc.author.facultyΠολυτεχνική Σχολή / Faculty of Engineering
dc.author.departmentΤμήμα Μηχανικών Μηχανολογίας και Κατασκευαστικής / Department of Mechanical and Manufacturing Engineering
dc.type.uhtypeArticleen
dc.contributor.orcidStylianopoulos, T. [0000-0002-3093-1696]
dc.description.totalnumpages2426-2431
dc.gnosis.orcid0000-0002-3093-1696


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record