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

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.

SUBMITTER: Kheirolomoom A

PROVIDER: S-EPMC4688109 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Kheirolomoom Azadeh A Ingham Elizabeth S ES Mahakian Lisa M LM Tam Sarah M SM Silvestrini Matthew T MT Tumbale Spencer K SK Foiret Josquin J Hubbard Neil E NE Borowsky Alexander D AD Murphy William J WJ Ferrara Katherine W KW

Journal of controlled release : official journal of the Controlled Release Society 20151022 Pt A

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. Where ...[more]

PMID: 26471394

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

Publications

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

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