CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery. Academic Article uri icon


  • 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.

published proceedings

  • J Control Release

altmetric score

  • 1

author list (cited authors)

  • Kheirolomoom, A., Ingham, E. S., Mahakian, L. M., Tam, S. M., Silvestrini, M. T., Tumbale, S. K., ... Ferrara, K. W.

citation count

  • 23

complete list of authors

  • Kheirolomoom, Azadeh||Ingham, Elizabeth S||Mahakian, Lisa M||Tam, Sarah M||Silvestrini, Matthew T||Tumbale, Spencer K||Foiret, Josquin||Hubbard, Neil E||Borowsky, Alexander D||Murphy, William J||Ferrara, Katherine W

publication date

  • January 2015