Chall Amy, Stagg John, Mixson Andrew, Gato Eric, Quirino Rafael L, Sittaramane Vinoth
Department of Biology, Georgia Southern University, Statesboro, GA 30460, United States of America.
Department of Chemistry and Biochemistry, Georgia Southern University, Statesboro, GA 30460, United States of America.
Nanotechnology. 2021 May 7;32(19):195102. doi: 10.1088/1361-6528/abe32a.
This is a proof-of-principle study on the combination of microwaves and multiwalled carbon nanotubes to induce in vivo, localized hyperthermic ablation of cells as a potential methodology for the treatment of localized tumors. Compared to conventional methods, the proposed approach can create higher temperatures in a rapid and localized fashion, under low radiation levels, eliminating some of the unwanted side effects. Following successful ablation of cancer cells in cell culture and zebrafish tumor-xenograft models, it is hypothesized that a cancer treatment can be developed using safe microwave irradiation for selective ablation of tumor cells in vivo using carbon nanotube-Antibody (CNT-Ab) conjugates as a targeting agent. In this study, mice were used as an animal model for the optimization of the proposed microwave treatment strategy. The safe dose of CNT-Ab and microwave radiation levels for mice were determined. Further, CNT-Ab distribution and toxicology in mice were qualitatively determined for a time span of two weeks following microwave hyperthermia. The results indicate no toxicity associated with the CNT-Ab in the absence of microwaves. CNTs are only found in the proximity of the site of injection and have been shown to effectively cause hyperthermia induced necrosis upon exposure to microwaves with no noticeable damage to other tissues that are not in direct contact with the CNT-Ab. To understand the cellular immune response towards CNT-Abs, transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to assay for their ability to phagocytize CNT-Ab. Our results indicate that macrophages and neutrophils were able to actively phagocytose CNT-Abs shortly after injection. Taken together, this is the first study to show that CNTs can be used in combination with microwaves to cause targeted ablation of cells in mice without any side effects, which would be ideal for cancer therapies.
这是一项原理验证研究，旨在探索微波与多壁碳纳米管相结合，在体内诱导细胞局部热消融，作为治疗局部肿瘤的一种潜在方法。与传统方法相比，该方法能够在低辐射水平下，以快速且局部的方式产生更高的温度，从而消除一些不良副作用。在细胞培养和斑马鱼肿瘤异种移植模型中成功消融癌细胞后，研究假设可以开发一种癌症治疗方法，即使用安全的微波辐射，以碳纳米管 - 抗体（CNT - Ab）偶联物作为靶向剂，在体内选择性消融肿瘤细胞。在本研究中，使用小鼠作为动物模型来优化所提出的微波治疗策略。确定了小鼠的CNT - Ab安全剂量和微波辐射水平。此外，在微波热疗后的两周时间内，定性测定了小鼠体内CNT - Ab的分布和毒理学。结果表明，在没有微波的情况下，CNT - Ab没有毒性。碳纳米管仅在注射部位附近被发现，并且已证明在暴露于微波时能有效引起热诱导坏死，而对未与CNT - Ab直接接触的其他组织没有明显损伤。为了了解细胞对CNT - Ab的免疫反应，使用带有荧光标记巨噬细胞和中性粒细胞的转基因斑马鱼来检测它们吞噬CNT - Ab的能力。我们的结果表明，巨噬细胞和中性粒细胞在注射后不久就能主动吞噬CNT - Ab。综上所述，这是第一项表明碳纳米管可与微波结合，在小鼠体内实现细胞靶向消融且无任何副作用的研究，这对于癌症治疗将是理想的。
