CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery

Azadeh Kheirolomoom, Elizabeth S. Ingham, Lisa M. Mahakian, Sarah M. Tam, Matthew T. Silvestrini, Spencer K. Tumbale, Josquin Foiret, Neil Hubbard, Alexander D Borowsky, William J Murphy, Katherine W. Ferrara

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Ultrasonic activation of nanoparticles provides the opportunity to deliver a large fraction of the injected dose to insonified tumors and produce a complete local response. Here, we evaluate whether the local and systemic response to chemotherapy can be enhanced by combining such a therapy with locally-administered CpG as an immune adjuvant. In order to create stable, activatable particles, a complex between copper and doxorubicin (CuDox) was created within temperature-sensitive liposomes. Whereas insonation of the CuDox liposomes alone has been shown to produce a complete response in murine breast cancer after 8 treatments of 6 mg/kg delivered over 4 weeks, combining this treatment with CpG resolved local cancers within 3 treatments delivered over 7 days. Further, contralateral tumors regressed as a result of the combined treatment, and survival was extended in systemic disease. In both the treated and contralateral tumor site, the combined treatment increased leukocytes and CD4+ and CD8+ T-effector cells and reduced myeloid-derived suppressor cells (MDSCs). Taken together, the results suggest that this combinatorial treatment significantly enhances the systemic efficacy of locally-activated nanotherapy.

Original languageEnglish (US)
Pages (from-to)253-264
Number of pages12
JournalJournal of Controlled Release
Volume220
DOIs
StatePublished - Dec 28 2015

Keywords

  • CpG
  • Doxorubicin
  • Immunotherapy
  • Temperature-sensitive liposome
  • Ultrasound

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Kheirolomoom, A., Ingham, E. S., Mahakian, L. M., Tam, S. M., Silvestrini, M. T., Tumbale, S. K., Foiret, J., Hubbard, N., Borowsky, A. D., Murphy, W. J., & Ferrara, K. W. (2015). CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery. Journal of Controlled Release, 220, 253-264. https://doi.org/10.1016/j.jconrel.2015.10.016