12.1 Introduction

Photothermal cancer therapy, also called photothermal therapy (PTT), uses light‐induced heat to treat cancer cells. PTT has attracted attention owing to its advantages over traditional cancer therapies such as chemotherapy, radiation therapy (RT), and surgery. Thermal therapy was discovered during the nineteenth century when cancer patients were administered living bacteria to cause inflammation and subsequent fever. The use of circulating heated water to treat uterine cervical cancer was also reported during that era. Owing to the rudimentary technology of that age, neither clinical applications nor further studies of thermal therapy were explored. Interest in PTT was revived in the 1980s, and owing to the fast development of optical and nanomaterial technology during recent decades, thermal therapy, particularly PTT has become a fast‐growing field of study [1–5].

Unlike traditional thermal therapies, PTT is a relatively mild cancer therapy that primarily uses a hyperthermia treatment administered at temperatures of 41 °C–48 °C [6]. Several cellular reactions take place within this temperature range, including (i) protein denaturation and aggregation, which destroy cellular homeostasis and lower cell survival rates; (ii) cell inactivation for several hours or more at temperatures above 42 °C but below 45 °C, which can increase oxidative stress and subsequently damage proteins, lipids, and nucleic acids, after which cells undergo apoptosis or secondary necrosis processes; and (iii) rapid cellular necrosis at temperatures above 45 °C. Although, as noted by Fuente [7], direct necrosis initiated by hyperthermia can cause bodily inflammation, which should be avoided in the clinical treatment of cancer; useful applications of hyperthermia therapy could induce cell death via cellular apoptosis and secondary necrosis, which do not cause an inflammatory response.

Another factor that limits the clinical application of PTT is the lack of effective light for thermal triggering owing to the intrinsic absorbance by water and hemoglobin and the light‐scattering effect of body tissue [6]. These tissue properties result in the poor penetration of visible light at the tumor site, thereby limiting heat triggering. This effect can be illustrated with the spectrum shown in Figure 12.1.

Because of light‐wave extinction by tissue, visible light is unsuitable for PTT applications. However, intrinsic tissue absorption and scattering of light is relatively lower between the wavelengths of 700 and 1400 nm. Light in this region can be divided into two parts: (i) a first bio‐window of 700–980 nm, in which the absorbance by water significantly vanishes but residual scattering persists; and (ii) a second bio‐window of 1000–1400 nm, in which absorbance does not completely vanish but scattering is minimized. Most light‐triggered therapies use lasers within the bio‐windows to achieve deeper tissue penetration and avoid the side effects of normal tissue heating.

To achieve precise heating within the tumor region and avoid the heating of noncancerous tissue, PTT must deliver an efficient thermal reagent to the tumor site that can be triggered by a bio‐window laser to produce heat. Rapid developments in nanotechnology have allowed the study of dozens of nanomaterials, including metallic and semiconducting materials [4, 8], organic polymers [9], carbon nanomaterials [10], and quantum dots (QDs) [11] for both in vitro and in vivo PTT. Carbon nanomaterials are good choices for photothermal reagents because they have (i) relatively higher absorbance in the two bio‐windows described above, (ii) good biocompatibility, (iii) easily modified and functionalized surfaces, and (iv) good dispersibility in bio‐liquids, particularly blood.

Carbon nanomaterials include carbon nanodiamonds and graphite structural nanomaterials. Carbon nanodiamonds have not yet proved efficient for photothermal conversion. However, graphite structural nanomaterials, including graphene oxide (GO) [12], carbon nanotubes (CNTs) [13], carbon nanohorns (CNHs) [14], carbon dots (CDs) [15], graphene dots (GDs) [16], and fullerenes [17] have been widely studied for photothermal applications. In graphite structural nanomaterials, a π‐plasmon absorbance background at the bio‐windows and relatively lower luminance are the mechanisms for good light‐to‐heat conversion efficiency. Therefore, these materials are efficient photothermal reagents. Oxygen‐containing functional groups (particularly carboxyl) produced during synthesis impart hydrophilic and other easily modified properties to graphite structural nanomaterials. Moreover, the stability of their carbon structures and good solubility in bio‐fluids, which aid their ultimate elimination from the body, give graphite structural nanomaterials good biocompatibility.

Liu studied nano‐sized GO (nGO) for in vivo PTT in animals and observed that 24 hours after tail vein injection, nGO accumulated at tumor sites owing to enhanced permeability and retention (EPR), whereas little accumulation occurred in other organs with the exception of the kidneys [12]. In addition to GO, other graphite structural nanomaterials, particularly CNTs, have been studied for applications in PTT [18].

Combinations of carbon nanomaterials with reagents and other nanomaterials for magnetic resonance imaging [19], computed tomography [20], or photoacoustic or Raman imaging [21, 22] have also been studied for imaging‐guided PTT, which is also called theranostics. Because the surfaces of carbon nanomaterials can be easily modified, derived drug loading and biomolecular functionalization are avenues for further combination therapy with chemotherapy, photodynamic therapy, RT, gene therapy, immune therapy, and other modalities.

Given the diversity of carbon nanomaterials, the compatibility of these materials for combination therapy with PTT, and the large number of studies aimed at developing effective photothermal applications for carbon nanomaterials, the aim of this chapter is to provide an overview of the carbon nanomaterials useful for PTT and their current PTT applications. The following topics are covered:

• GO for PTT
• CNTs and CNHs for PTT
• CDs and GDs for PTT
• Fullerenes for PTT
• Carbon nanomaterial‐based nanocomposites for PTT
• Carbon nanomaterial‐based combined therapy with PTT

12.2 GO for PTT

GO, a two‐dimensional carbon nanomaterial, has been studied as a nanomedicine for biomedical applications. As mentioned in the introduction, extinction at the near‐infrared (NIR) windows limits the photothermal applications of nanomaterials. However, GO is an effective PTT reagent owing to its intrinsic absorption in the NIR region, efficient cellular uptake, and easy preparation. Because GO is easily modified, a variety of GO‐based nanomaterials have been developed for cancer and theranostic therapies.

12.2.1 PTT‐Related Physical and Chemical Properties of GO

The aromatic structure of GO suggests that strong optical absorbance in the NIR region will result in NIR light‐triggered photothermal conversion. However, because carbon atoms in GO nanosheets are partially oxidized to sp³ carbon atoms during synthesis, its absorbance is likely to be weaker than that of grapheme [23, 24]. According to Yang et al., the reduction of GO increases NIR region absorbance three‐ to fourfold and significantly improves photothermal conversion (Figure 12.2) [25].

Furthermore, the carboxyl groups generated on GO during synthesis impart hydrophilic properties, which are vital in biomedical applications. However, the reduction process substantially consumes carboxyl groups, which reduces the dispersibility of reduced GO (rGO). Therefore, additional surface modifications have been investigated to improve the dispersibility of rGO. For example, polyethylene glycol (PEG)‐grafted poly(maleic anhydride‐alt‐1‐octadecene) is directly grafted to the GO surface to improve the dispersibility of rGO, and dopamine is used to reduce GO via coating on the rGO surface to prevent rGO aggregation [9, 26].

12.2.2 GO for in vitro PTT

To assess the in vitro effects of various photothermal reagents, researchers have constructed temperature increase curves by directly measuring the temperatures generated under continuous laser irradiation. Photothermal conversion efficiency is primarily calculated according to the method reported by Roper et al. [27].

Because it has excellent photothermal conversion efficiency, GO and functionalized GO have been widely investigated for in vitro PTT applications. PEG is usually used to improve the dispersibility and stability of GO in the physiological environment [25, 28]. GO easily enters cells and locates in the cytoplasm; however, cellular uptake efficiency can be improved through the use of a positively charged polymer such as polyethyleneimine (PEI) [29–31]. PEI reverses the surface charge of GO, which improves interactions with cell membranes. Fluorescent dyes such as rhodamine B [32] are used to modify the GO surface so that it can be traced for intracellular behavior studies.

Initially, researchers tried to reduce GO to improve its photothermal conversion efficiency. The partially rGO partly removed the oxygen‐containing groups, thereby significantly improving NIR absorbance and photothermal conversion efficiency. Another way to improve photothermal conversion efficiency is to combine GO with other photothermal reagents. For example, an NIR cyanine dye was used to enhance the absorbance of GO and thereby increase photothermal conversion efficiency [33]. Because the interaction between GO and the cyanine dye is sensitive to ambient pH, the absorbance enhancement is dependent on pH; therefore, the GO–cyanine dye system has been designed for pH‐triggered photothermal enhancement, which is accompanied by a pH detection function (Figure 12.3) [22].

As illustrated above, significant efforts have been made to improve the photothermal performance of GO. We believe that a good photothermal reagent should have the following properties:

• High NIR absorbance
• High photothermal conversion efficiency
• Good stability in the biotic environment
• Efficient cellular uptake
• Good biocompatibility

In most PTT‐related studies, the 3‐(4, 5‐dimethylthiazol‐2‐yl) 2, 5‐diphenyl tetrazolium bromide (MTT) assay is used to assess the cytotoxicity of photothermal reagents and evaluate biocompatibility [22, 32–34]. Some of these studies have evaluated the toxicity of photothermal reagents, including carbon nanomaterials [35–37]. PEG, chitosan, bovine serum albumin, poly(acrylic acid), and polydopamine (PDA) have been used to modify GO to reduce its cytotoxicity [25, 26, 38–40]. According to a study by Cheng, biopolymers including PDA‐, bovine serum albumin‐, and heparin‐grafted GO show ultralow cytotoxicity even at concentrations of 100 μg ml⁻¹ .

The NIR light used for in vitro studies of carbon nanomaterial‐based PTT varies from less than 0.5 W cm⁻² to more than 10 W cm⁻² . However, the maximum permissible exposure to lasers in NIR‐1 is 0.33 W cm⁻² (808 nm) and that for lasers in NIR‐2 is 1 W cm⁻² (1000–1100 nm) (ANSI Z136.1.2007, American National Standard for Safe Use of Lasers). Therefore, researchers have attempted to improve photothermal conversion efficiency to decrease the laser intensity required for PTT. Yang et al. reported that the use of NIR‐808 nm at a laser intensity of 0.15 W cm⁻² is effective for in vitro and in vivo photothermal cancer therapy [25].

For evaluating in vitro cancer cell cytotoxicity, the MTT assay is most widely used for quantified assessments, and fluorescence staining is most often used for qualitative evaluations. Surface modification technology is used to increase cell uptake of nanomaterials. For example, cancer cell‐specific aptamers, permeable peptides, folic acid, biotin, and other molecules have been used to modify carbon nanomaterials for this purpose [32, 41–43].

Cytotoxicity studies examine both cell death caused by photothermal effects and cell responses to PTT. Yang et al. showed that for GO, photothermal effects kill cells via apoptosis and the cell response to hypothermal damage is the overexpression of heat shock proteins (HSPs) to maintain homeostasis [32]. Two HSP family members, HSP90 and HSP70, are overexpressed during photothermal treatment (Figure 12.4). However, this HSP overexpression cannot completely mitigate the thermal damage and the decompensatory stage occurs nonetheless. Therefore, cells undergo apoptosis, which may result in secondary necrosis that is expected to be beneficial for clinical PTT applications because it causes the least inflammation [7].

12.2.3 GO for in vivo PTT

For in vivo applications, GO must be protected from aggregation in the circulatory system. PEGylation is the most widely used GO modification for achieving good stability. Multi‐armed PEG has also been used to enhance stability [25].

Solid tumors under the skin are the most frequently used in vivo models for studies of PTT with GO. Both intratumor and intravenous injections have been used to expose tumors to nanomaterials. NIR illumination is performed after a large amount of nanomaterial aggregates in the tumor via the EPR effect. Although studies have used various nanomaterial concentrations and NIR intensities, most have achieved successful tumor ablation or inhibition. Yang et al. modified a nanographene sheet (NGS) with PEG and conjugated it to an NIR dye to study its in vivo behavior in mice [44]. After intravenous injection, NGS was maintained primarily in the tumor; the amount of NGS stranded in reticuloendothelial systems, including the spleen and liver, was much lower. After subsequent NIR irradiation, the tumors were easily eliminated, and hematoxylin and eosin staining of tissue slides, which is used in many PTT studies, showed no organ damage two days after the disappearance of the tumor (Figure 12.5).

12.3 CNTs and CNHs for PTT

CNTs have optical absorbance in the NIR region. Unlike GO, however, they have a long, hollow architecture prepared by rolling graphene. CNTs can be either single‐walled (SWCNTs) or multi‐walled (MWCNTs), and each type has different properties and specific photothermal effects. Owing to their needle‐like structures, CNTs are easily taken up by cells. CNHs are hollow tubules of single‐walled grapheme tubules, which are similar to CNTs and possess short and conically shaped structures [14]. CNHs are capable of absorbing NIR light, leading to significant photothermal effects. This characteristic enhances their biomedical applications, including those in PTT.

12.3.1 Physical and Chemical Properties of CNTs and CNHs Related to PTT

The intrinsic absorbance of CNTs and CNHs in the NIR region are much higher than that of water, which is the main source of heat produced in tissues under NIR illumination (Figure 12.6) [45]. As reported by Torti, MWCNTs allow for greater photothermal conversion and cancer cell killing [46]. CNHs exhibit many advantages over other nanomaterials and serve as promising candidates for PTT. Their size (50–100 nm) is optimal for enhanced penetration and retention effect, leading to excess accumulation at tumor sites [47, 48]. CNHs are more biocompatible than many other nanomaterials requiring metal catalyst [49]. The efficient cellular uptake in tumors and high biocompatibility make CNH a better candidate for PTT than CNT.

Although still widely studied, SWCNTs and SWCHNs are not the most efficient carbon nanomaterials for photothermal conversion. According to a study by Trajkovic, the capacity for photothermal cell killing of GO is higher than that of CNTs [50]. There are several reasons for this difference, including the superior photothermal sensitivity and better dispersibility of GO. The poor dispersibility of CNTs and CNHs greatly limits their biomedical application. Therefore, CNTs and CNHs must be modified with hydrophilic polymers to disperse well in physiological environments. Many studies have aimed to improve the performance of CNTs in PTT by introducing hydrophilicity via polymer addition. Among these polymers, the most widely used is PEG, which is nontoxic but interferes with cell processes [51–53].

12.3.3 CNTs and CNHs for in vivo PTT

The in vivo applications of CNTs and CNHs in PPT have also been widely studied, particularly those of functionalized CNTs, which have superior PTT performance [8, 13, 64, 65]. According to the studies by Liu and other researchers, well‐dispersed CNTs efficiently eliminate in vivo solid tumors at very low NIR intensities [66, 67]. Raman scattering analysis has shown that injected CNTs exhibit ultra‐high retention in tumors (Figure 12.7). Choi and coworkers demonstrated exceptional in vivo biocompatibility of PEG‐functionalized SWCNTs and survival longer than six months in a mouse model [68]. In this model, intravenously injected SWCNTs were primarily excreted through the liver and kidneys.

CNHs have been combined along with NIR laser irradiation to reduce the tumor size in vivo, demonstrating their PTT ability [65]. CHN‐induced photothermal tumor ablation can be achieved without triggering any adverse effects on normal tissues [60]. Thermal‐ and CHN‐treated patients showed hair growth at one week after treatment without tumor recurrence (Figure 12.8). These studies provided evidence of the safety of CNTs and CNHs in PTT and other biomedical applications.

12.4 CDs and GDs for PTT

The small size and fluorescent properties of CDs and GDs distinguish them from other carbon nanomaterials. Furthermore, the synthetic methods (both top‐down and bottom‐up methods have been developed) and sources for CDs and GDs are also diverse and abundant; therefore, the properties of different CDs or GDs can vary significantly. Benefiting from ultrasmall size and hydrophilic properties, CDs and GDs can be easily dispersed in medium and taken up by cells. Compared with the biocompatibility of semiconductor QDs, that CDs and GDs is superior for biomedical applications, and because they contain aromatic groups, they are also suitable for drug loading and PTT. These properties, combined with their fluorescent properties and ease of surface modification, make CDs and GDs appropriate for theranostic applications.

12.4.1 Physical and Chemical Properties of CDs and GDs Related to PTT

The average size of CDs and GDs is less than 10 nm, with most being approximately 2–5 nm [15, 69, 70]. This small size allows for direct penetration into cells and extensive cellular uptake. Because synthetic routes to CDs and GDs are abundant, a variety of surface properties and modifications are possible [15, 70, 71]. A positively charged surface and residual surface functional groups are beneficial for nanomaterial–cell interactions.

For PTT applications, photothermal conversion effects are of primary importance. The optical absorbance of CDs varies in the NIR region. Zhang found only weak prolonged absorbance from π–π* interactions in the NIR region [72]. However, Jing described a CD synthesized from hydrophobic cyanine dye and PEG via the solvothermal process and showed that its photothermal conversion efficiency reached approximately 38.7%, which is higher than that of graphitic pencil nanodots (27%; Figure 12.9) [15]. The increased photothermal conversion efficiency may originate with the residual functional groups on the CD surface. To increase the photothermal effects, researchers usually use other nanomaterials to prepare nanocomposites with CDs and GDs [16, 73–77].

12.4.2 CDs and GDs for in vitro PTT

Because CDs have high solubility, their surfaces require no modifications with hydrophilic molecules to improve dispersibility. Furthermore, the fluorescent properties of CDs are advantageous in biomedical applications because they allow for simultaneous tumor imaging and NIR‐triggered thermal therapy [15, 71, 78]. Fluorescence also aids the monitoring of the intracellular behavior of CDs. Both CDs and GDs can also be used for photoacoustic imaging. Therefore, in vitro PTT studies of CDs usually include cellular imaging analyses. Benefiting from easy surface modification, CDs are often functionalized with aptamers and drugs. Furthermore, because the synthesis of CDs and GDs is flexible, a wide range of element‐doped CDs and GDs with various properties have also been developed for photothermal applications. For example, Lee et al. synthesized CDs with different degrees of nitride doping to enhance photothermal conversion efficiency (Figure 12.10) [69]. An N content of 7 M saturated the CDs and maximized photothermal conversion efficiency. Zhang synthesized B‐doped GDs for simultaneous T₁‐weighted imaging and PTT applications [79].

12.4.3 CDs and GDs for in vivo PTT

Because CDs are fluorescent, their in vivo behavior can be studied directly. Wang reported that after intravenous injection, CDs circulate in the blood without aggregation and accumulate in tumors via the EPR effect [71]. The results of a body distribution study showed that most CDs were located in the tumor.

Another concern for in vivo PTT is the distribution of nanomaterials in reticuloendothelial system organs. Although a large portion of CDs is retained in the liver, compared with the accumulation in the tumor, this proportion is negligible and no tissue damage has been observed. The intratumor temperature reaches 57 °C under NIR₆₇₁ illumination at a power density of 2 W cm⁻² (Figure 12.11).

Recently, Lan et al. used two‐photon‐excited NIR‐emissive CDs for in vivo PTT [80]. Under 880 nm NIR illumination at 0.5 W for six minutes, the intratumor temperature reached 52 °C and tumor growth was effectively inhibited.

12.5 Fullerenes for PTT

Fullerenes have poor solubility, limiting their applications in the biomedical field. To solve this major problem, various functional fullerenes have been developed using chemical modifications on their surface [81, 82]. The potential of functional fullerenes has been demonstrated in cancer treatment, including photodynamic therapy, PTT, and chemotherapy [81] and tumor diagnosis (magnetic resonance and photoacoustic imaging).

12.5.2 Fullerenes for in vitro PTT

Because fullerenes have poor solubility, their surfaces require modifications for improved dispersibility. Krishna et al. reported that polyhydroxy fullerenes (PHF) and carboxy fullerenes can be heated under low‐intensity NIR laser irradiation (785 nm). PHF‐coated silica nanoparticles were dosed onto mesothelial lung carcinoma cells. After 10 seconds of NIR laser irradiation, bubbles formed, and floating cellular fragments were immediately observed (Figure 12.12). These results clearly indicate that NIR laser triggered the photothermal effects of PHF, further supporting the notion that these nanomaterials can effectively eliminate cancer cells in vitro [86].

12.5.3 Fullerenes for in vivo PTT

PHFs are water‐soluble, rapidly excreted and biodegradable carbon nanoparticle, and have antioxidant, and neuroprotective properties in living organisms [17, 86]. These properties make PHF an ideal candidate for cancer PTT. After chitosan‐PHF nanoparticles were injected and exposed to NIR laser, tumors in a cross‐sectional area decreased by an average of 32% within 2 hours of treatment, with only a blister visible 20 hours post‐treatment (Figure 12.13) [17]. Therefore, PHF may enable the safe and effective use of PTT for various cancer types.

12.6 Carbon Nanomaterial‐Based Nanocomposites for PTT

Owing to their robust performance in PTT applications, carbon nanomaterials have attracted strong interest for combinations with other nanomaterials or reagents for multifunctional performance. Easy surface functionalization and robust interaction with other reagents allow easy synthesis of carbon nanomaterials into nanocomposites. For example, the carboxyl groups on the surface of GO make it amenable to the amidation reaction and CDs synthesized from various reagents with surface functional groups offer potential for further modification. Nanocomposites are most often used to achieve enhanced PTT effects and develop multifunctional nanomedicines and are synthesized accordingly.

12.6.1 GO‐Based Nanocomposites for PTT

Good dispersibility, presence of surface carboxyl groups, and large surface area allow GO to react and form nanocomposites easily under appropriate conditions. Currently, a wide variety of nanocomposites are based on GO. In addition to the use of chemical reagents such as glucose, dopamine, or citric acid to produce rGO, noble metals such as gold, compound such as CuS, and NIR dyes such as cypate have been used to synthesize GO nanocomposites with enhanced photothermal effects, including greater photothermal conversion [22, 32, 88]. Yun et al. synthesized a nanocomposite of gold nanorods (AuNRs), iron oxide, and GO [89]. AuNRs show enhanced absorbance in the NIR region owing to the longitudinal surface plasmon resonance of free electrons along the elongated axis, and iron oxide has absorbance in the NIR region as well. The NIR absorbance and photothermal effects of this GO nanocomposite are significantly higher than those of GO alone (Figure 12.14).

Dembereldorj et al. used an AuNR‐PEG‐GO nanocomposite for PTT and achieved efficient in vitro cancer cell killing and in vivo tumor growth inhibition [90]. Fe₃O₄ nanoparticles have also been used to synthesize GO composites with enhanced photothermal effects [77]. Arginine and cypate have been combined with rGO to enhance NIR absorbance [22, 91].

Beyond the use of other nanomaterials to enhance the photothermal conversion efficiency, the cytotoxicity of nanocomposites can be improved by increasing the capacity to cause cell death (apoptosis). For example, Yu et al. used a peptide to functionalize PDA‐modified rGO to increase cancer cell death via the bystander effect triggered by PTT [26].

12.7 Carbon Nanomaterial‐Based Combined Therapy with PTT

12.8 Conclusions and Perspectives

From a summary of the literature in this section, different carbon nanomaterials have both tumor detection and cancer‐cell−killing capabilities. These characteristics result in carbon nanomaterials have huge developmental potential in cancer treatment. Specific carbon nanomaterials, such as graphene, have extremely large surface areas that can be loaded with siRNA, DNA, or other biological molecules and chemotherapy drugs, thereby endowing them with capabilities of drug delivery and gene transfection. In relevant in vitro and in vivo studies on cancer photohyperthermia, it can be seen that carbon nanomaterials have good NIR photothermal conversion efficiency. In addition, the drug delivery and test capabilities of carbon nanomaterials can result in synergistic therapeutic effects during cancer treatment and decrease damage due to normal cells during treatment. As carbon nanomaterials have unique optical characteristics, many studies have used it in photodynamic therapy in cancer cells. The above characteristics have enabled carbon nanomaterials to become the next generation of cancer therapy drugs with the greatest developmental potential.

In our opinion, GO, CDs, and CNHs have great potential for PTT development attributable to their superior relevant physical and chemical characteristics. GO is an effective PTT reagent because of its intrinsic NIR absorption capability, efficient cellular uptake, and easy preparation. Reduction of GO can be used to increase the NIR region absorbance and improve photothermal conversion. NIR absorption and photothermal conversion effects are of primary importance for PTT. CDs and GDs are effective in PTT applications because of their high solubility, efficient cellular uptake, and abundant synthetic routes. Moreover, fluorescent properties of CDs are advantageous in biomedical applications because they allow for simultaneous tumor imaging and PTT. CNHs are particularly effective because of their intrinsic NIR absorption, efficient cellular uptake, and high biocompatibility. CHNs are produced by laser ablation of graphite, hence, there is no toxicity associated with the presence of metal catalysts.

It is necessary to carry out further relevant clinical and translational medicine studies before carbon nanomaterials can be used in the treatment of actual cancers. In addition, it is worth noting that progress in animal safety evaluation studies on carbon nanomaterials lags far behind studies on other cancer therapies and this has resulted in a controversy on the biological safety of carbon nanomaterials. The results of some studies have found that carbon nanomaterials have high biocompatibility. However, the studies of some researchers have also proven that exposure to carbon nanomaterials may result in different degrees of biological toxic effects to living organisms. Our research team carried out an evaluation of biological toxicity of GO and rGO and found that these two carbon nanomaterials may affect the normal immune function of biological organisms. The biological toxicity and relevant physical and chemical characteristics of carbon nanomaterials, such as particle size, surface charge, and specific surface modification are intimately connected. Therefore, we must carry more and deeper safety evaluation studies on carbon nanomaterials, including evaluation of biocompatibility and pharmacodynamics (absorption, distribution, metabolism, and elimination, ADME) to further address current safety concerns of carbon nanomaterials in cancer therapy applications.

Undoubtedly, carbon nanomaterials are one of the most researched and most promising drugs in cancer photohyperthermia. During the high development process of carbon nanomaterials, we must pay more attention to potential biological toxicity risk to ensure the biological safety of carbon nanomaterials during cancer photohyperthermia treatment and increase the feasibility of carbon nanomaterials in cancer therapy applications.

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