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dc.contributor.authorSuh, SeungBeum
dc.contributor.authorJo, Ami
dc.contributor.authorTraore, Mahama A.
dc.contributor.authorZhan, Ying
dc.contributor.authorCoutermarsh-Ott, Sheryl L.
dc.contributor.authorRingel-Scaia, Veronica M.
dc.contributor.authorAllen, Irving C.
dc.contributor.authorDavis, Richey M.
dc.contributor.authorBehkam, Bahareh
dc.date.accessioned2018-12-20T15:04:40Z
dc.date.available2018-12-20T15:04:40Z
dc.date.issued2018-12-05
dc.identifier.urihttp://hdl.handle.net/10919/86455
dc.description.abstractCancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor‐targeting S. Typhimurium VNP20009 are interfaced with poly(lactic‐co‐glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self‐replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100‐fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.en_US
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen_US
dc.publisherWileyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBacteria-based therapiesen_US
dc.subjectbiohybrid systemsen_US
dc.subjectextravascular transporten_US
dc.subjectintratumoral penetrationen_US
dc.subjecttumor-targeting bacteriaen_US
dc.titleNanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicineen_US
dc.typeArticle - Refereeden_US
dc.title.serialAdvanced Scienceen_US
dc.identifier.doihttps://doi.org/10.1002/advs.201801309
dc.type.dcmitypeText


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Attribution 4.0 International
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