Cancer Cell Coating Nanoparticles for Optimal Tumor-Specific Cytokine Delivery

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Abstract
Although cytokine therapy is an attractive strategy to build a more robust immune response in tumors, cytokines have faced clinical failures due to toxicity. In particular, interleukin-12 has shown great clinical promise but was limited in translation due to systemic toxicity. In this study, we demonstrate an enhanced ability to reduce toxicity without affecting efficacy of IL-12 therapy. We engineer the material properties of a NP to meet the enhanced demands for optimal cytokine delivery by using the layer-by-layer (LbL) approach. Importantly, using LbL, we demonstrate cell-level trafficking of NPs to preferentially localize to the cell’s outer surface and act as a drug depot, which is required for optimal payload activity on neighboring cytokine membrane receptors. LbL-NPs showed efficacy against a tumor challenge in both colorectal and ovarian tumors at doses that were not tolerated when administered carrier-free.
Funding Information
  • National Cancer Institute (1-R01-CA235375-01A1)
  • Division of Graduate Education (1122374)
  • Alfred P. Sloan Foundation
  • Massachusetts Institute of Technology
  • Congressionally Directed Medical Research Programs (W81XWH-13-1-0151)
  • Thomas and Stacey Siebel Foundation
  • U.S. Department of Education (GR26419)
  • Frost Environmental Science/Studies Fund (EN347700)
  • Marble Center for Cancer Nanomedicine, Massachusetts Institute of Technology
  • Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

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