Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles
Name
c8bm01208c.pdf
Size
3.52 MB
Format
Adobe PDF
Checksum (MD5)
b1a080f4951fc0e7f7c4ed60d73ad8aa
Author(s)
Bekdemir, Ahmet
Watson, Nicki
Ingram, Jessica
Stellacci, Francesco R.
Yang, Yu-Sang Sabrina
Moynihan, Kelly Dare
Dichwalkar, Tanmay M
Noh, Michelle M.
Melo, Mariane Bandeira
Suh, Heikyung
Date Issued
November 2018
Journal
Biomaterials Science
Publisher
Royal Society of Chemistry
Citation
Yang, Yu-Sang Sabrina, Kelly D. Moynihan, Ahmet Bekdemir, Tanmay M. Dichwalkar, Michelle M. Noh, Nicki Watson, Mariane Melo, et al. “Targeting Small Molecule Drugs to T Cells with Antibody-Directed Cell-Penetrating Gold Nanoparticles.” Biomaterials Science 7, no. 1 (2019): 113–124. © The Royal Society of Chemistry
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution Noncommercial 3.0 unported license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/c8bm01208c
