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

JOURNAL OF CONTROLLED RELEASE

卷:220

Article

Kheirolomoom, Azadeh¹  Ingham, Elizabeth S.¹  Mahakian, Lisa M.¹  Tam, Sarah M.¹  Silvestrini, Matthew T.¹  Tumbale, Spencer K.¹  Foiret, Josquin¹  Hubbard, Neil E.²  Borowsky, Alexander D.²  Murphy, William J.³  Ferrara, Katherine W.¹ 

[1] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA

[2] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA

[3] Univ Calif Davis, Dept Dermatol, Inst Regenerat Cures, Sacramento, CA 95817 USA

关键词: CpG;    Doxorubicin;    Temperature-sensitive liposome;    Ultrasound;    Immunotherapy;   

DOI  :  10.1016/j.jconrel.2015.10.016

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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