Pancreatic tumor microenvironmental acidosis and hypoxia transform gold nanorods into cell-penetrant particles for potent radiosensitization

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dc.citation.articleNumbereabm9729en_US
dc.citation.issueNumber45en_US
dc.citation.journalTitleScience Advancesen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorRauta, Pradipta Ranjanen_US
dc.contributor.authorMackeyev, Yurien_US
dc.contributor.authorSanders, Keithen_US
dc.contributor.authorKim, Joseph B.K.en_US
dc.contributor.authorGonzalez, Valeria V.en_US
dc.contributor.authorZahra, Yasminen_US
dc.contributor.authorShohayeb, Muhammad A.en_US
dc.contributor.authorAbousaida, Belalen_US
dc.contributor.authorVijay, Geraldine V.en_US
dc.contributor.authorTezcan, Okanen_US
dc.contributor.authorDerry, Paulen_US
dc.contributor.authorLiopo, Anton V.en_US
dc.contributor.authorZubarev, Eugene R.en_US
dc.contributor.authorCarter, Rickeyen_US
dc.contributor.authorSingh, Pankajen_US
dc.contributor.authorKrishnan, Sunilen_US
dc.date.accessioned2022-12-13T19:11:38Zen_US
dc.date.available2022-12-13T19:11:38Zen_US
dc.date.issued2022en_US
dc.description.abstractCoating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.en_US
dc.identifier.citationRauta, Pradipta Ranjan, Mackeyev, Yuri, Sanders, Keith, et al.. "Pancreatic tumor microenvironmental acidosis and hypoxia transform gold nanorods into cell-penetrant particles for potent radiosensitization." <i>Science Advances,</i> 8, no. 45 (2022) AAAS: https://doi.org/10.1126/sciadv.abm9729.en_US
dc.identifier.digitalsciadv-abm9729en_US
dc.identifier.doihttps://doi.org/10.1126/sciadv.abm9729en_US
dc.identifier.urihttps://hdl.handle.net/1911/114128en_US
dc.language.isoengen_US
dc.publisherAAASen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titlePancreatic tumor microenvironmental acidosis and hypoxia transform gold nanorods into cell-penetrant particles for potent radiosensitizationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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