期刊
ACS NANO
卷 14, 期 9, 页码 11238-11253出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c03109
关键词
nanomedicine; immuno-oncology; nanoparticle; drug delivery; layer-by-layer; cytokine
类别
资金
- Koch Institute Core Grant from the NCI [P30-CA14051]
- U.S. Department of Defense Congressionally Directed Medical Research Programs [W81XWH13-1-0151]
- Koch Institute for Integrative Cancer Research at MIT [1-R01CA235375-01A1]
- Dana-Farber/Harvard Cancer Center, NIH [1-R01CA235375-01A1]
- Marble Center for Cancer Nanomedicine
- Cancer Center Support (core) Grant from the National Cancer Institute [P30CA14051]
- Koch Institute's Marble Center for Cancer Nanomedicine Fellowship
- Sloan UCEM Fellowship
- Siebel Scholars Fellowship
- National Science Foundation [GFRP 1122374]
- MIT Undergraduate Research Opportunity Office
- Frost Environmental Science/Studies Fund [EN34770]
- Ronald E. McNair PostBaccalaureate Achievement Program [GR26419]
- NIH interdepartmental biotechnology training program [5T32GM008334-30]
- Koch Institute from the National Cancer Institute [P30-CA14051]
- MIT MRSEC Shared Experimental Facilities Grant from the National Science Foundation [DMR-0819762]
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 because of systemic toxicity. In this study, we demonstrate an enhanced ability to reduce toxicity without affecting the 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.
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