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Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors
McDaid, William J Lissin, N. Pollheimer, E. Greene, M. Leach, A. Smyth, P. Bossi, G. Longley, D. Cole, D. K. Scott, C. J.
McDaid, William J
Lissin, N.
Pollheimer, E.
Greene, M.
Leach, A.
Smyth, P.
Bossi, G.
Longley, D.
Cole, D. K.
Scott, C. J.
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Abstract
For effective targeted therapy of cancer with chemotherapy-loaded nanoparticles (NPs), antigens that are selective for cancer cells should be targeted to minimise off-tumour toxicity. Human leukocyte antigens (HLAs) are attractive cancer targets as they can present peptides from tumour-selective proteins on the cell surface, which can be recognised by T cells via T cell receptors (TCRs). In this study, docetaxel-loaded polymeric NPs were conjugated to recombinant affinity-enhanced TCRs to target breast cancer cells presenting a tumour-selective peptide-HLA complex. The TCR-conjugated nanoparticles enabled enhanced delivery of docetaxel and induced cell death through tumour-specific peptide-HLA targeting. These in vitro data demonstrate the potential of targeting tumour-restricted peptide-HLA epitopes using high affinity TCR-conjugated nanoparticles, representing a novel treatment strategy to deliver therapeutic drugs specifically to cancer cells.
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Date
2021
Publisher
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Article
Citation
McDaid WJ, Lissin N, Pollheimer E, Greene M, Leach A, Smyth P, et al. Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors. Nanoscale. 2021;13(35):15010–20.