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

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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.

Graphical abstract: Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles

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Publication details

The article was received on 01 Oct 2018, accepted on 09 Nov 2018 and first published on 13 Nov 2018


Article type: Paper
DOI: 10.1039/C8BM01208C
Citation: Biomater. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles

    Y. S. Yang, K. D. Moynihan, A. Bekdemir, T. M. Dichwalkar, M. M. Noh, N. Watson, M. Melo, J. Ingram, H. Suh, H. Ploegh, F. R. Stellacci and D. J. Irvine, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01208C

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