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dc.contributor.advisorFernandes, Rohanen_US
dc.contributor.authorCano-Mejia, Julianaen_US
dc.date.accessioned2016-02-09T06:34:13Z
dc.date.available2016-02-09T06:34:13Z
dc.date.issued2015en_US
dc.identifierhttps://doi.org/10.13016/M2P99C
dc.identifier.urihttp://hdl.handle.net/1903/17364
dc.description.abstractMultifunctional nanoparticles represent a class of materials with diverse therapy and imaging properties that can be exploited for the treatment of cancers that have significantly progressed or advanced, which are associated with a poor patient prognosis. Here, we describe the use of biodegradable Prussian blue nanoparticles (PBNPs) in combination with anti-CTLA-4 checkpoint blockade immunotherapy for the treatment of advanced cancers. Our nanoparticle synthesis scheme yields PBNPs that possess pH-dependent intratumoral stability and photothermal therapy (PTT) properties, and degrade under mildly alkaline conditions mimicking the blood and lymph. Studies using PBNPs for PTT in a mouse model of neuroblastoma, a hard-to-treat cancer, demonstrate that PTT causes rapid reduction of tumor burden and growth rates, but results in incomplete responses to therapy and tumor relapse. Studies to elucidate the underlying immunological responses demonstrate that PTT causes increased tumor infiltration of lymphocytes and T cells and a systemic activation of T cells against re-exposed tumor cells in a subset of treated mice. PBNP-based PTT in combination with anti-CTLA-4 immunotherapy results in complete tumor regression and long-term survival in 55.5% of neuroblastoma tumor-bearing mice compared to only 12.5% survival in mice treated with anti-CTLA-4 alone and 0% survival both in mice treated with PTT alone, or remaining untreated. Further, all of the combination therapy-treated mice exhibit protection against tumor rechallenge indicating the development of antitumor immunity as a consequence of therapy. Our studies indicate the immense potential of our combination photothermal immunotherapy in improving the prognosis and outlook for patients with advanced cancers.en_US
dc.language.isoenen_US
dc.titleBiodegradable Prussian blue nanoparticles for photothermal immunotherapy of advanced cancersen_US
dc.typeThesisen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentBioengineeringen_US
dc.subject.pqcontrolledBiomedical engineeringen_US
dc.subject.pqcontrolledNanotechnologyen_US
dc.subject.pqcontrolledImmunologyen_US
dc.subject.pquncontrolledanti-CTLA-4en_US
dc.subject.pquncontrolledcanceren_US
dc.subject.pquncontrolledphotothermal immunotherapyen_US
dc.subject.pquncontrolledPrussian blue nanoparticlesen_US


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