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    Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent

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    Issue Date
    2020-09-25
    Author
    Groer, Chad
    Zhang, Ti
    Lu, Ruolin
    Cai, Shuang
    Mull, Derek
    Huang, Aric
    Forrest, Melanie
    Berkland, Cory
    Aires, Daniel
    Forrest, Marcus Laird
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2020 American Chemical Society
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    Abstract
    A carrier-based, immunogenic cell death (ICD)-eliciting platinum(IV) chemotherapeutic agent was synthesized via complexation between an axially derivatized Pt(IV)-tocopherol and hyaluronan (HA)–tocopherol nanocarrier. The resultant HA-Pt(IV) complex demonstrated antiproliferative activity and induced calreticulin translocation, an indicator of ICD, in murine and human head and neck cancer (HNC) cells. The intratumorally administered HA-Pt(IV) treatments were tolerable and efficacious in both immunocompetent and immunodeficient mice with HNC, partially because of the direct cytotoxicity. Superior efficacy and survival were observed in the immunocompetent group, suggesting a possible Pt(IV)-induced immunological response, which would only manifest in animals with an intact immune system. Subsequent imaging of tumor tissues demonstrated increased macrophage infiltration in the HA-Pt(IV)-treated tumors compared to the nontreated controls and the cisplatin-treated tumors, suggesting favorable inflammatory activation. RNA sequencing of HA-Pt(IV)-treated tumors indicated that carbohydrate and vitamin metabolisms were the most important Kyoto Encyclopedia of Genes and Genomes pathways, and molecular function, biological process, and cellular component were highly enriched gene ontology categories.
    Description
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.0c00781.
    URI
    http://hdl.handle.net/1808/32421
    DOI
    https://doi.org/10.1021/acs.molpharmaceut.0c00781
    Collections
    • Pharmaceutical Chemistry Scholarly Works [314]
    Citation
    Groer, C., Zhang, T., Lu, R., Cai, S., Mull, D., Huang, A., Forrest, M., Berkland, C., Aires, D., & Forrest, M. L. (2020). Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent. Molecular pharmaceutics, 17(11), 4334–4345. https://doi.org/10.1021/acs.molpharmaceut.0c00781

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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