Photothermal therapy of papillary thyroid cancer tumor xenografts with targeted thyroid stimulating hormone receptor antibody functionalized multiwalled carbon nanotubes

Abstract

AbstractMultiwalled carbon nanotubes (MWCNTs) are being widely investigated in multiple biomedical applications including, and not limited to, drug delivery, gene therapy, imaging, biosensing, and tissue engineering. Their large surface area and aspect ratio in addition to their unique structural, optical properties, and thermal conductivity also make them potent candidates for novel hyperthermia therapy. Here we introduce thyroid hormone stimulating receptor (TSHR) antibody–conjugate–MWCNT formulation as an enhanced tumor targeting and light-absorbing device for the photoablation of xenografted BCPAP papillary thyroid cancer tumors. To ensure successful photothermal tumor ablation, we determined three key criteria that needed to be addressed: (1) predictive pre-operational modeling; (2) real-time monitoring of the tumor ablation process; and (3) post-operational follow-up to assess the efficacy and ensure complete response with minimal side effects. A COMSOL-based model of spatial temperature distributions of MWCNTs upon selected laser irradiation of the tumor was prepared to accurately predict the internal tumor temperature. This modeling ensured that 4.5W of total laser power delivered over 2 min, would cause an increase of tumor temperature above 45 ℃, and be needed to completely ablate the tumor while minimizing the damage to neighboring tissues. Experimentally, our temperature monitoring results were in line with our predictive modeling, with effective tumor photoablation leading to a significantly reduced post 5-week tumor recurrence using the TSHR-targeted MWCNTs. Ultimately, the results from this study support a utility for photosensitive biologically modified MWCNTs as a cancer therapeutic modality. Further studies will assist with the transition of photothermal therapy from preclinical studies to clinical evaluations.