Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors.
William J McDaidNikolai LissinEllen PollheimerMichelle GreeneAdam LeachPeter SmythGiovanna BossiDaniel LongleyDavid K ColeChristopher J ScottPublished in: Nanoscale (2021)
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.
Keyphrases
- cancer therapy
- drug delivery
- cell death
- papillary thyroid
- locally advanced
- photodynamic therapy
- cell surface
- breast cancer cells
- regulatory t cells
- endothelial cells
- dendritic cells
- squamous cell
- oxidative stress
- wound healing
- walled carbon nanotubes
- high glucose
- rectal cancer
- lymph node metastasis
- climate change
- signaling pathway
- risk assessment
- artificial intelligence
- peripheral blood
- cell cycle arrest
- pi k akt
- data analysis
- replacement therapy