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Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity.

Publication ,  Journal Article
Mastria, EM; Cai, LY; Kan, MJ; Li, X; Schaal, JL; Fiering, S; Gunn, MD; Dewhirst, MW; Nair, SK; Chilkoti, A
Published in: J Control Release
January 10, 2018

Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined. We report herein that Chimeric Polypeptide Doxorubicin (CP-Dox), a nanoparticle formulation of doxorubicin, enhances antitumor immunity. Compared to free doxorubicin, a single intravenous (IV) administration of CP-Dox at the maximum tolerated dose increases the infiltration of leukocytes into the tumor, slowing tumor growth and preventing metastasis in poorly immunogenic 4T1 mammary carcinoma. We demonstrate that the full efficacy of CP-Dox is dependent on CD8+ T cells and IFN-γ. CP-dox treatment also repolarized intratumoral myeloid cells towards an antitumor phenotype. These findings demonstrate that a nanoparticle drug is distinct from the free drug in its ability to productively stimulate antitumor immunity. Our study strongly argues for the use of antitumor immunotherapies combined with nanoparticle-packaged chemotherapy.

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Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

January 10, 2018

Volume

269

Start / End Page

364 / 373

Location

Netherlands

Related Subject Headings

  • Pharmacology & Pharmacy
  • Peptides
  • Nanoparticles
  • Mice, Inbred BALB C
  • Mammary Neoplasms, Experimental
  • Interferon-gamma
  • Female
  • Drug Compounding
  • Doxorubicin
  • Cell Line, Tumor
 

Citation

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Mastria, E. M., Cai, L. Y., Kan, M. J., Li, X., Schaal, J. L., Fiering, S., … Chilkoti, A. (2018). Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity. J Control Release, 269, 364–373. https://doi.org/10.1016/j.jconrel.2017.11.021
Mastria, Eric M., Leon Y. Cai, Matthew J. Kan, Xinghai Li, Jeffrey L. Schaal, Steven Fiering, Michael D. Gunn, Mark W. Dewhirst, Smita K. Nair, and Ashutosh Chilkoti. “Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity.J Control Release 269 (January 10, 2018): 364–73. https://doi.org/10.1016/j.jconrel.2017.11.021.
Mastria EM, Cai LY, Kan MJ, Li X, Schaal JL, Fiering S, et al. Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity. J Control Release. 2018 Jan 10;269:364–73.
Mastria, Eric M., et al. “Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity.J Control Release, vol. 269, Jan. 2018, pp. 364–73. Pubmed, doi:10.1016/j.jconrel.2017.11.021.
Mastria EM, Cai LY, Kan MJ, Li X, Schaal JL, Fiering S, Gunn MD, Dewhirst MW, Nair SK, Chilkoti A. Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity. J Control Release. 2018 Jan 10;269:364–373.
Journal cover image

Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

January 10, 2018

Volume

269

Start / End Page

364 / 373

Location

Netherlands

Related Subject Headings

  • Pharmacology & Pharmacy
  • Peptides
  • Nanoparticles
  • Mice, Inbred BALB C
  • Mammary Neoplasms, Experimental
  • Interferon-gamma
  • Female
  • Drug Compounding
  • Doxorubicin
  • Cell Line, Tumor