Format

Send to

Choose Destination
J Control Release. 2015 Dec 28;220(Pt A):253-264. doi: 10.1016/j.jconrel.2015.10.016. Epub 2015 Oct 22.

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

Author information

1
University of California, Davis, Department of Biomedical Engineering, 451 East Health Sciences Drive, Davis, CA 95616, USA.
2
University of California, Davis, Center for Comparative Medicine, Davis, CA 95616, USA.
3
University of California, Davis, Department of Dermatology, 2921 Stockton Blvd., Institute for Regenerative Cures, Suite 1630, Sacramento, CA 95817, USA.
4
University of California, Davis, Department of Biomedical Engineering, 451 East Health Sciences Drive, Davis, CA 95616, USA. Electronic address: kwferrara@ucdavis.edu.

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.

KEYWORDS:

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

PMID:
26471394
PMCID:
PMC4688109
DOI:
10.1016/j.jconrel.2015.10.016
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center