Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer

Corrine Ying Xuan Chua, Priya Jain, Antonia Susnjar, Jessica Rhudy, Marco Folci, Andrea Ballerini, April Gilbert, Shailbala Singh, Giacomo Bruno, Carly S. Filgueira, Cassian Yee, E. Brian Butler, Alessandro Grattoni

Research output: Contribution to journalArticle

Abstract

Conventional systemic immunotherapy administration often results in insufficient anti-tumor immune response and adverse side effects. Delivering immunotherapeutics intratumorally could maximize tumor exposure, elicit efficient anti-tumor immune response, and minimize toxicity. To fulfill the unmet clinical need for sustained local drug delivery and to avoid repeated intratumoral injections, we developed a nanofluidic-based device for intratumoral drug delivery called the nanofluidic drug-eluting seed (NDES). The NDES is inserted intratumorally using a minimally invasive trocar method similar to brachytherapy seed insertion and offers a clinical advantage of drug elution. Drug diffusion from the NDES is regulated by physical and electrostatic nanoconfinement, thereby resulting in constant and sustained immunotherapeutic delivery without the need for injections or clinician intervention. In this study, the NDES was used to deliver immunotherapeutics intratumorally in the 4 T1 orthotopic murine mammary carcinoma model, which recapitulates triple negative breast cancer. We demonstrated that NDES-mediated intratumoral release of agonist monoclonal antibodies, OX40 and CD40, resulted in potentiation of local and systemic anti-tumor immune response and inhibition of tumor growth compared to control mice. Further, mice treated with NDES-CD40 demonstrated minimal liver damage compared to systemically treated mice. Collectively, our study highlights the NDES as an effective platform for sustained intratumoral immunotherapeutic delivery. The potential clinical impact is tremendous given that the NDES is applicable to a broad spectrum of drugs and solid tumors.

Original languageEnglish
Pages (from-to)23-34
Number of pages12
JournalJournal of Controlled Release
Volume285
DOIs
Publication statusPublished - Sep 10 2018
Externally publishedYes

Keywords

  • CD40 agonist antibody
  • Immunotherapy
  • Intratumoral drug delivery
  • OX40 agonist antibody
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Chua, C. Y. X., Jain, P., Susnjar, A., Rhudy, J., Folci, M., Ballerini, A., Gilbert, A., Singh, S., Bruno, G., Filgueira, C. S., Yee, C., Butler, E. B., & Grattoni, A. (2018). Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer. Journal of Controlled Release, 285, 23-34. https://doi.org/10.1016/j.jconrel.2018.06.035