Nanofluidic delivery implant sustains localization and maximizes efficacy of intratumoral immunotherapy

Hsuan Chen Liu, Nicola Di Trani, Marzia Conte, Dinh Chuong Nguyen, Simbarashe Jokonya, Abe Wu, Robin Vander Pol, Ashley L. Joubert, Ilaria Facchi, Anthony M. Wood, Jeremy Ho, Federica Pesaresi, Valentina Cauda, Shu Hsia Chen, Xuewu Liu, Patrick S. Stayton, Corrine Ying Xuan Chua, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review


Intratumoral immunotherapy holds promise for improving cancer treatment efficacy. However, rapid clearance from the tumor upon bolus volume injections limits efficacy and impedes assessment of dose-dependent effects on the tumor immune microenvironment (TIME). To this end, we developed a drug-agnostic nanofluidic implant to deliver immunotherapy within the tumor, providing a mechanism for sustained and controlled intratumoral dosing. Diffusive drug elution from the implant reservoir is controlled by a nanofluidic membrane, which abrogates rapid drug elimination from the tumor and maximizes immunotherapy localization. Here we first achieve in vitro sustained release of agonist CD40 monoclonal antibody (mAb), anti-programmed death ligand-1 (PDL1) mAb, and immune-cell targeted polymeric prodrugs of Resiquimod (toll-like receptor 7/8,TLR 7/8) and a small molecule STING agonist. We then demonstrated in vivo sustained intratumoral drug localization of agonist CD40 Ab and anti-PDL1 Ab in the 4T1 murine model of triple-negative breast cancer (TNBC). Further, we show highly effective anti-tumor efficacy with radiation therapy and sustained intratumoral co-delivery of agonist CD40 Ab and anti-PDL1 Ab in the EMT6 TNBC murine model. Finally, we demonstrate the versatility of this implant by showing that sustained intratumoral delivery of the STING or Resiquimod polymeric prodrugs strongly inhibits 4T1 tumor growth. Collectively, these results support our nanofluidic system as a therapeutic platform technology to investigate sustained intratumoral dosing of immunotherapy.

Original languageEnglish (US)
Article number102258
JournalNano Today
StatePublished - Jun 2024


  • Controlled release
  • Drug delivery
  • Immune checkpoint inhibitors
  • Intratumoral immunotherapy
  • Nanofluidic implant
  • STING agonist
  • Toll-like receptor agonist

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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