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

Authors
  • A, Kheirolomoom
  • Es, Ingham
  • Lm, Mahakian
  • Sm, Tam
  • Mt, Silvestrini
  • Sk, Tumbale
  • J, Foiret
  • Ne, Hubbard
  • Ad, Borowsky
  • William Murphy
  • Kw, Ferrara
Type
Published Article
Journal
Journal of Controlled Release
Publisher
Elsevier
Volume
220
Issue
Pt A
Pages
253–253
Identifiers
DOI: 10.1016/j.jconrel.2015.10.016
Source
Murphy Lab dermatology-ucdavis
License
Unknown

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.

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