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Nanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine

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dc.contributor.authorSuh, SeungBeumen
dc.contributor.authorJo, Amien
dc.contributor.authorTraore, Mahama Azizen
dc.contributor.authorZhan, Yingen
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorRingel-Scaia, Veronica M.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorDavis, Richey M.en
dc.contributor.authorBehkam, Baharehen
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentChemical Engineeringen
dc.contributor.departmentMacromolecules Innovation Instituteen
dc.date.accessioned2018-12-20T15:04:40Zen
dc.date.available2018-12-20T15:04:40Zen
dc.date.issued2018-12-05en
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
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1002/advs.201801309en
dc.identifier.urihttp://hdl.handle.net/10919/86455en
dc.language.isoenen
dc.publisherWileyen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBacteria-based therapiesen
dc.subjectbiohybrid systemsen
dc.subjectextravascular transporten
dc.subjectintratumoral penetrationen
dc.subjecttumor-targeting bacteriaen
dc.titleNanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicineen
dc.title.serialAdvanced Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Macromolecules Innovation Institute (MII)
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