RRC ID 72177
Author Barberio AE, Smith SG, Correa S, Nguyen C, Nhan B, Melo M, Tokatlian T, Suh H, Irvine DJ, Hammond PT.
Title Cancer Cell Coating Nanoparticles for Optimal Tumor-Specific Cytokine Delivery.
Journal ACS Nano
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 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.
Volume 14(9)
Pages 11238-11253
Published 2020-9-22
DOI 10.1021/acsnano.0c03109
PMID 32692155
PMC PMC7530125
MeSH Cytokines Drug Delivery Systems Humans Nanoparticles* Neoplasms* / drug therapy
IF 14.588
Resource
Human and Animal Cells OV2944-HM-1(RCB1483)