期刊
JOURNAL OF CONTROLLED RELEASE
卷 220, 期 -, 页码 253-264出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2015.10.016
关键词
CpG; Doxorubicin; Temperature-sensitive liposome; Ultrasound; Immunotherapy
资金
- [NIHR01CA134659]
- [NIHR01CA103828]
- [NIHR01CA199658]
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. (C) 2015 Elsevier B.V. All rights reserved.
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