title: Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.
abstract: BACKGROUND
  The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches.
  
  
  METHODS
  Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining.
  
  
  RESULTS
  TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls.
  
  
  CONCLUSIONS
  A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with fewer side effects and improved quality of life.
authors.affiliation: Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Idit
authors.initials: I
authors.lastname: Dotan
authors.affiliation: Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Roche
authors.affiliation: Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.|Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Paliouras
authors.affiliation: Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.|Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Elliot J
authors.initials: EJ
authors.lastname: Mitmaker
authors.affiliation: Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.|Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Trifiro
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D002277:Carcinoma / Q000628:therapy*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D028022:Low-Level Light Therapy / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000819:agonists / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000819:agonists / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000628:therapy*; D057073:Thyrotropin Alfa / Q000494:pharmacology*
chemical_list: D000912:Antibodies, Neoplasm; D037742:Nanotubes, Carbon; D009363:Neoplasm Proteins; D011989:Receptors, Thyrotropin; D057073:Thyrotropin Alfa