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Biomater Sci. 2018 Dec 18;7(1):113-124. doi: 10.1039/c8bm01208c.

Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles.

Author information

1
Massachusetts Institute of Technology, Department of Materials Science and Engineering, Cambridge, 02139, USA. djirvine@mit.edu.

Abstract

We sought to develop a nanoparticle vehicle that could efficiently deliver small molecule drugs to target lymphocyte populations. The synthesized amphiphilic organic ligand-protected gold nanoparticles (amph-NPs) were capable of sequestering large payloads of small molecule drugs within hydrophobic pockets of their ligand shells. These particles exhibit membrane-penetrating activity in mammalian cells, and thus enhanced uptake of a small molecule TGF-β inhibitor in T cells in cell culture. By conjugating amph-NPs with targeting antibodies or camelid-derived nanobodies, the particles' cell-penetrating properties could be temporarily suppressed, allowing targeted uptake in specific lymphocyte subpopulations. Degradation of the protein targeting moieties following particle endocytosis allowed the NPs to recover their cell-penetrating activity in situ to enter the cytoplasm of T cells. In vivo, targeted amph-NPs showed 40-fold enhanced uptake in CD8+ T cells relative to untargeted particles, and delivery of TGF-β inhibitor-loaded particles to T cells enhanced their cytokine polyfunctionality in a cancer vaccine model. Thus, this system provides a facile approach to concentrate small molecule compounds in target lymphocyte populations of interest for immunotherapy in cancer and other diseases.

PMID:
30444251
PMCID:
PMC6310171
DOI:
10.1039/c8bm01208c
[Indexed for MEDLINE]
Free PMC Article

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