Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells

Abstract

BackgroundThe 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.MethodsThyroid 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.ResultsTSHR-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.ConclusionA 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.

Prostate-specific membrane antigen–directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells

“…Presently, a high level of biological and chemical functionalization potential is available for binding of targeting ligands to MWCNT nanoparticles, thus mediating cancer cell recognition and subsequent nearfield cell ablation. Expanding on our previous study 20 of MWCNT nanoparticle-mediated targeting strategy, here we specifically target prostate-specific membrane antigen (PSMA) expressed in CaP cells by optimizing the nanoparticle functionalization and antibody conjugation chemistry. We also aimed to show that highly efficient targeting should place a sufficient number of nanoparticles directly on the surface of cells so as to deliver exquisite extreme nearfield heat energy sufficient for cell ablation without bulk heating.…”

<p>Role of Nanofluids in Drug Delivery and Biomedical Technology: Methods and Applications</p>

“…The results of this study showed that, with increasing the concentrations of ZnO NPs in 48 and 72 hours of treatment, the survival rate of MCF-7 cell lines in breast cancer decreased. Dotan et al 44 developed a nanofluid platform by conjugating multi-walled carbon nanotubes (CNTs) with either thyroid-specific antibody or thyroid-stimulating hormone. The nanofluid selectively targeted and killed the papillary thyroid cancer cells in vitro with minimal cytotoxic effect on the non-targeted cells.…”

Practical applications of studies on the TSH receptor and TSH receptor autoantibodies

“…A different novel strategy to control thyroid cancer includes targeting the TSHR with nano-liposomes coated with fragments of TSH and loaded with chemotherapeutic agents [24]. Another proposed approach is based on using TSHR binding carbon-walled nanotubes, which have the ability to convert external light energy to heat energy resulting in killing the cancer cells locally [25]. Also, small molecule antagonist to the TSHR would offer yet another approach to inhibit thyroid cancer progression by suppressing TSHR signalling [26].…”