New progress in carbon nanotubes in the diagnosis and treatment of tumors

New progress in carbon nanotubes in the diagnosis and treatment of tumors

Cai Shaoyu Kong Jilie 3

(Biomedical Research Institute, Department of Chemistry, Fudan University, Shanghai 200433)

Abstract Carbon nanotubes have a unique structure and properties and are widely used in biomedical fields. This paper reviews the research status of carbon nanotubes in biomedical, especially early diagnosis and treatment of tumors, analyzes the existing research characteristics, and looks forward to the development trend in this field.

Key words carbon nanotubes, carbon nanohorn, biomedical, tumor, diagnosis, treatment, review

1 Introduction

Carbon nanotubes (CNTs) have been discovered since 1991 ^[1] , with their unique structure and excellent thermal, electrical and mechanical properties such as large specific surface area, good heat transfer, electrical conductivity and high mechanical properties. The intensity has caused widespread concern and has become a research hotspot in the field of nanomaterials. A large amount of research work shows that carbon nanotubes have great application potential in electronic devices, composite materials, hydrogen storage materials, chemical and biological sensors. In recent years, the application of carbon nanotubes in biomedicine, especially on drug carriers, has gradually become a new hot spot ^{[2 ~ 6]} . As the incidence of cancer has increased year by year, although the treatment methods have improved, the survival rate has improved. However, the mortality rate remains high, and traditional diagnostic and therapeutic methods still have many shortcomings. Therefore, more effective and safe means are needed to achieve early diagnosis and treatment of tumors ^{[7 ~ 10] Â}  . This paper reviews the research status of carbon nanotubes in the field of biomedicine, especially early diagnosis and treatment of tumors, analyzes the existing research characteristics, and forecasts the development trend of this research field.

2 tumor cell diagnosis

2.1 resonance imaging

The application of contrast agents (CAs) in magnetic resonance imaging (MR I) technology is more and more widely used, and can be divided into three categories due to their different magnetic properties: paramagnetic, superparamagnetic and ferromagnetic materials, and based on carbon nanomaterials. Magnetic resonance imaging contrast agents are mainly concentrated in the first two categories.

2. 1. 1 Paramagnetic paramagnetic contrast agent is mainly composed of ruthenium chelates. Due to the unpaired electrons, Gd ^{3 +} is paramagnetic, thus shortening the longitudinal relaxation time of protons in the surrounding water. Hashimoto et al. ^[11] reported a new method for selectively depositing Gd ^{3 +} in hydrophilic pores of carbon nanohorns (Fig. 1a). Carbon nanohorns (CNHs) are a special type of single-walled carbon nanotubes (SWNTs) with a conical cap-like end and exist in a radial aggregate state. Due to defects in the cap-like end and the tube wall, the carbon tube can be destroyed by oxidation to cause voids to accumulate Gd ^{3 +} in the form of oxides in the center of the carbon nanohorn ^[11] . Sitharaman et al ^[12] conducted a similar study, depositing CdCl3 into ultrashort SWNTs (Fig. 1b), which is 40 to 90 times more relaxed than commercial contrast agents, and its imaging performance is greatly improved, presumably carbon. The tube is caused by the restriction of the metal ion cluster in the tube. Subsequent studies ^[13] demonstrated that the complex is extremely sensitive to pH in the range of pH 7. 0 to 7.4. Because of the difference in pH between cancerous tissue and normal tissue, it is expected to be applied to the early diagnosis of tumors. Richard et al ^[14] adsorbed the amphiphilic metal ruthenium chelate on multi-walled carbon nanotubes (MWNTs). The complex not only has the paramagnetism of the positive contrast agent, but also causes a negative signal enhancement in the T2 weight image of the animal experiment. It is presumed that the movement of the electrons in the carbon tube wall causes the magnetic moment to cause the carbon tube itself to have a magnetic induction. Due to the large length of the carbon nanotubes, in order to meet the requirements of molecular imaging, the length of the carbon nanotubes needs to be shortened in order to facilitate the absorption of cells, improve biocompatibility and achieve ultimate elimination in vivo.

2. 1. 2 superparamagnetic

Superparamagnetic iron oxide (SPIO) has also received extensive attention due to its large magnetic susceptibility and low toxicity. Miyawaki et al. ^[15] deposited Fe3O4 onto the surface of oxidized carbon nanohorns to form superparamagnetic carbon nanohorns. Animal experiments have shown that the magnetic nanohorns signal is significantly attenuated in magnetic resonance imaging, and the signal changes over time in the spleen and kidney. When the dose is below 8 mg/kg, it does not show any toxicity to small animals. Although magnetic resonance imaging has a high spatial resolution, its low sensitivity limits its application in biomedical and molecular imaging. It is an effective way to develop contrast agents with higher imaging performance. With its good transfer capacity and special space limitation on contrast molecules, carbon nanotubes have broad application prospects in magnetic resonance imaging.

2. 2 near infrared imaging

Since organisms do not substantially emit fluorescence in the near-infrared region (NIR), but SWNTs produce intense fluorescence, they can be detected in complex biological environments. The literature [16, 17 ] proves that SWNTs can still observe their near-infrared fluorescence signals after entering the cells, thereby studying the changes in the pharmacokinetic behavior signals of carbon tubes after injection into small animals without affecting the normal growth of cells. In the case of the marker as long as 3 months ^[17] . Choi et al ^[19] used a DNA-encapsulated composite of carbon nanotube ferrite to form a bifunctional compound with magnetic resonance imaging and near-infrared fluorescence imaging capabilities. Mouse macrophages incubated with this complex not only have MR I The signal, and the near-infrared fluorescence of the carbon nanotubes entering the interior of the cell, clearly reveals the boundaries of the cell. In addition to living cells, the near-infrared fluorescence of carbon tubes can also be applied to in vivo imaging. Leeuw et al. ^[20] used non-destructive imaging of SWNTs distributed in Drosophila in vivo using unique near-infrared fluorescence emitted by SWNTs (Fig. 2). The experimental results show that the ingested SWNTs have no adverse physiological effects on fruit flies. Welsher et al ^[21] modified Rituxan and Herception antibodies on the surface of SWNTs, respectively, to specifically target near-infrared imaging of cells with corresponding receptors on the surface, and the results showed that carbon nanotubes were restricted to non-specific linkages of organisms. In the case, due to the presence of antibodies, the near-infrared signals of different cells with different receptor expression have larger...

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