Dotan Idit, Roche Philip J R, Paliouras Miltiadis, Mitmaker Elliot J, Trifiro Mark A
Lady Davis Institute for Medical Research-Jewish General Hospital, Montreal, QC, Canada.
Department of Medicine, McGill University, Montreal, QC, Canada.
PLoS One. 2016 Feb 22;11(2):e0149723. doi: 10.1371/journal.pone.0149723. eCollection 2016.
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.
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.
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.
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.
在过去几十年中,甲状腺乳头状癌(PTC)的发病率以及复发率一直在稳步上升。有人提出,靶向消融物理疗法可能是甲状腺癌的一种治疗方式。靶向生物亲和功能化多壁碳纳米管(生物纳米流体)在局部起作用,能有效地将外部光能转化为热能,从而特异性地杀死癌细胞。这可能代表一种有前景的新型癌症治疗方式,超越了传统的激光消融和其他纳米颗粒方法。
由于甲状腺刺激激素受体(TSHR)广泛表达,故将其选为PTC细胞的靶点。TSHR抗体或促甲状腺素释放激素或纯化的促甲状腺激素(促甲状腺素)与我们功能化的生物纳米流体进行化学偶联。使用二极管激光系统(532纳米)对PTC细胞系进行设定曝光时间的照射。使用台盼蓝染色评估细胞死亡情况。
靶向TSHR的生物纳米流体能够选择性地消融TSHR阳性的PTC细胞系BCPAP,而对TSHR缺失的NSC - 34细胞无效。我们确定,BCPAP细胞与α - TSHR - 生物纳米流体的共轭比例为2:1且激光照射30秒时,约60%的BCPAP细胞被杀死,而使用促甲状腺素和促甲状腺素释放激素 - 生物纳米流体共轭物时,分别有65%和>70%的细胞被消融。此外,使用选择性对照观察到的非靶向杀伤极少。
已对为甲状腺乳头状癌提供潜在治疗途径的生物纳米流体平台进行了研究,我们的体外研究结果表明开发出了一种有效且快速的选择性癌细胞杀伤方法。因此,生物纳米流体治疗凸显了新技术对于治疗目前正在接受再次颈部探查手术、反复给予放射性碘以及作为最后手段进行外照射放疗或化疗的局部复发和转移性疾病患者的必要性,其副作用更少且生活质量更高。