@article{a93b982223544387872b67836a72158a,
title = "Polymer-coated carbon nanotubes as a molecular heater platform for hyperthermic therapy",
abstract = "Carbon nanotubes have been explored as heat-delivery vehicles for thermal ablation of tumors. To use single-walled carbon nanotubes (SWNT) as a “molecular heater” for hyperthermic therapy in cancer treatment, stable dispersibility and smart-targeting potential are necessary. The current study reports the dispersibility and exothermic properties with near-infrared (NIR) exposure for SWNT coated with a copolymer of N-isopropylacrylamide and polyethyleneglycol methacrylate (SWNT/PNIPAM-PEG-hybrid). The SWNT/PNIPAM-PEG hybrid showed stable dispersibility in PBS solution and exothermic potential with NIR exposure. Raman spectroscopy results revealed a hybrid derived Raman peak in mouse liver and spleen lysates for 7 days post-injection that disappeared by 14 days in all tissues (liver, spleen, heart, lung and kidney). These results suggested that the hybrid did not accumulate in mouse organ tissues in the long-term. The SWNT/PNIPAM-PEG hybrid decreased the cell viability (of mouse macrophages) with heat generation by NIR exposure. The results of this study demonstrate that the SWNT/PNIPAM-PEG hybrid is a useful platform for a “molecular heater” applicable to hyperthermic cancer therapy.",
author = "Koichiro Mori and Minoru Kawaguchi and Tsuyohiko Fujigaya and Jun Ohno and Tetsuro Ikebe",
note = "Funding Information: For therapeutic application of SWNT-based nanoparticles, the As mentioned above, the cross-linked PNIPAM-PEG coating did SWNT biodistribution profile after administration into animals should not affect the heat generation efficiency of the SWNT/PNIPAM-be addressed. From the results of biodistribution experiments using PEG hybrid. It is possible that if a monomer with functional groups, radiolabeled SWNTs, SWNTs showed high uptake in the liver and such as hydroxy, carboxyl, or imido groups, was copolymerized with spleen with low urinary excretion21). Although the radiolabeling method the PNIPAM-PEG, these functional groups may be introduced into is a convenient way to determine the biodistribution of SWNTs, the polymer coating layer. Ligands corresponding to the targeted excess free radioisotopes in the radiolabeled SWNT samples may lead protein can be introduced into the polymer coating layer via these to false results. In contrast, the intensity of the G-band of SWNTs{\textquoteright} functional groups. Thus, the hybrid is a useful antibody complex Raman spectrum is relatively insensitive to the diameter and bundling platform applicable for various types of antibodies in response to the nature of SWNTs. Furthermore, Raman spectroscopy can be used to corresponding target molecule. detect SWNTs in animals with high fidelity, without the concern of In summary, the SWNT/PNIPAM-PEG hybrid has potential as a radiolabeling falling off or decaying over time2). We thus used Raman nano-platform for molecular heating devices in hyperthermic therapy. spectroscopy to probe the biodistribution of SWNTs in various organs The intact side-wall structure, controlled tube length, and surface of mice. As shown in Fig. 3, a sharp Raman spectrum G-band peak coating with biocompatible PNIPAM-PEG copolymer make the hybrid was observed, and its linear dependence allowed for quantitative highly stable under biological conditions. Furthermore, the hybrid measurement of the SWNT/PNIPAM-PEG hybrids{\textquoteright} concentrations in showed suitable heat generation by NIR exposure, capable of inducing PBS solution. However, PBS solutions of the same concentrations of cell death. Although quantitative evaluation of the biodistribution DNA-SWNT showed no sharp G-band peak. This may be due to the in vivo could not be conducted, the hybrid did not show long-term partially destroyed surface structure of the DNA-SWNT. Liu et al. 22) accumulation in mouse organ tissues. The SWNT/PNIPAM-PEG hybrid evaluated the biodistribution of SWNT functionalized by branched is an appropriate molecular heating platform for hyperthermic devices. polyethyleneglycol (PEG) chains in mice over a period of three months by Raman spectrum measurement. They found that hydrophilic Acknowledgment functionalization, such as the PEG coatings, resulted in biologically The authors acknowledge Dr. Yusuke Tsutsumi and Ms. Yukiko inert SWNTs with long blood circulation, low RES (reticuloendothelial Nagai (Department of Applied Chemistry, Graduate School of system) uptake, and relatively fast clearance from organs. Although Engineering, Kyushu University), and Dr. Naotoshi Nakashima they detected the G-band peak in lysate tissues (liver and spleen) even 3 (International Institute for Carbon-Neutral Energy Research.WPI-months after injection, the SWNT concentrations in other organs (such I2CNER Kyushu University) for help with Raman analysis. This study as heart, lung and kidney) were below detection limits. We detected the was supported by JSPS KAKENHI Grant Number 16K11641. G-band peak in liver and spleen lysates for up to 7 days post-injection, but no appreciable Raman signals were detected in heart, lung or kidney tissues (Fig. 4). The Raman signal at 14 days post injection was not detectable for either the liver or spleen tissues. The total amount of the hybrid determined from the Raman signals for the liver and References spleen (7 days) indicated that approximately 95% of the hybrid was 1. Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X and Dai H. excreted within the first 7 days after injection. Although these findings Drug delivery with carbon nanotubes for in vivo cancer treatment. do not mean the absence of SWNT/PNIPAM-PEG hybrid accumulation Cancer Res 68: 6652-6660, 2008 in these organs after 14 days post-injection, it is possible that the 2. Liu Z, Tabakman S, Welsher K and Dai H. Carbon nanotubes in hybrid is rapidly excreted from the mouse body. As shown by several biology and medicine: In vitro and in vivo detection, imaging and biodistribution studies of SWNTs, appropriately functionalized SWNTs drug delivery. Nano Res 2: 85-120, 2009 Funding Information: The authors acknowledge Dr. Yusuke Tsutsumi and Ms. Yukiko Nagai (Department of Applied Chemistry, Graduate School of Engineering, 501100004096 Kyushu University), and Dr. Naotoshi Nakashima (International Institute for Carbon-Neutral Energy Research. WPII2CNER Kyushu University) for help with Raman analysis. This study was supported by Japan Society for the Promotion of Science JSPS KAKENHI Grant Number 16K11641. Publisher Copyright: {\textcopyright} 2018, Society of Hard Tissue Regenerative Biology. All rights reserved.",
year = "2018",
doi = "10.2485/jhtb.27.139",
language = "English",
volume = "27",
pages = "139--146",
journal = "Journal of Hard Tissue Biology",
issn = "1341-7649",
publisher = "Society of Hard Tissue Regenerative Biology",
number = "2",
}
