11.1 Introduction

Cancer has become a major cause of human mortality during the last few decades worldwide. Considering regional and global reports, increasing mortality rates of cancer appears as a primary stimulus to develop advanced diagnostic/therapeutic modalities to treat the disease much more effectively [1, 2]. Currently, the most common methods of cancer diagnosis include different imaging modalities such as single‐photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and mammography. They are used to provide effective detection of malignant sites in tissue/organs for improving the cancer prognosis [3, 4]. The commonly used therapeutic modalities (i.e. chemotherapy and radiotherapy) are often invasive and may inevitably elicit some undesired side effects in other healthy tissues/organs, which must be reduced/controlled by specific/selective targeting of the diseased cells/tissue with an advanced treatment modality. For enhancing therapies specifically/selectively on the target cells/tissue, the current trends are literally focused on targeted diagnosis and treatment of cancer simultaneously. In this line, various advanced multifunctional nanoparticles (NPs)/nanosystems (NSs) have been developed and successfully used for the concurrent detection and treatment of different tumors [5, 6]. Of these, NP‐based molecular probes armed with various imaging and targeting agents in combination with pH‐sensitive and photo/thermo‐responsive structure carrying therapeutic cargos have been developed as carriers to improve the efficacy of targeted diagnosis and therapy [7, 8].

Among deferent types of NPs, the carbon‐based NPs are considered as one of the most attractive nanomaterials that have been engineered in different forms, including single‐walled carbon nanotubes/multiple‐walled carbon nanotubes (SWCNTs/MWCNTs), nanohorns, fullerenes, nanodiamonds, carbon NPs, nanofibers, and graphene derivatives (Figure 11.1). So far, significant progress has been made for the synthesis, functionalization, and applications of the graphene‐based NSs in biomedicine, in large part because of the low‐cost of graphene and simplicity in terms of functionalization and surface modification. As carbon‐based advanced nanomaterial, the graphene‐based NSs have been used for the formulation of multifunctional nanomedicines and theranostics to serve as targeted drug delivery and imaging NSs. Graphene possesses hexagonally regular sp² hybridized carbon sheets structure with unique physicochemical properties, including high surface area, premier near infrared (NIR) absorption, and high electrical and heat conductivity. As a result, a large number of investigations have been conducted to be used in different biomedical applications such as carriers for drug delivery and targeting, scaffolds for cell/tissue engineering, biosensors, and NIR light absorbance in photothermal therapy/photodynamic therapy (PTT/PDT) [9, 10]. Depending on the biological applications of graphene, different types of functional groups can be grafted onto the graphene sheets to produce functionalized graphene. Owing to the large surface area and amphipathic nature of the graphene oxide (GO) developed by the oxidation of graphite sheets, it is considered as a promising flexible and biocompatible carbon‐based carrier for targeted detection, imaging, and therapy of cancer with extremely minimal cytotoxicity (Figure 11.1).

Graphene‐based materials can be fabricated by several approaches, among which the Hummer method is one of the most popular preparation approaches because it is very cost‐effective and facile scalable. GO can be reduced (e.g. by hydrazine hydrate) resulting in reduced graphene oxide (rGO). The characterization of GO can be accomplished by several techniques, including Furrier transform infrared (FT‐IR) spectroscopy, ultraviolet‐visible (UV‐Vis) spectroscopy, X‐ray diffraction (XRD), Raman scattering, scanning electron microscopy (SEM), field emission scanning electron microscope (FESEM), and other electrical measurements.

11.2 Multifunctional Graphene‐Based Composites for the Diagnosis/Therapy of Cancer

Graphene, GO, rGO, and its derivatives are considered as promising materials for cancer monitoring and biosensing due to their various features such as potent UV absorption, fluorescence quenching capability and functionalizable surface (see Figure 11.2) [13]. Further, these materials can be functionalized with various functional groups (e.g. carboxyl, hydroxyl, epoxy, etc.), which makes them as a hydrophilic substrate with trivial intrinsic toxicity and good dispersibility in the physiologic fluids [14]. By far, nanocomposites (NCs) of graphene‐based materials have been developed through modification with deferent types of biocompatible agents and nanoparticles (e.g. magnetic nanoparticles, gold nanoparticles, polymers, proteins, and etc.), resulting in the production of multifunctional NSs for in vitro and in vivo applications in drug delivery, tissue engineering, and multimodal diagnosis/therapy [15]. Furthermore, to maximize the impacts of chemotherapies, the PTT and PDT potential of graphene‐based materials have been combined with the cytotoxic effects of different chemotherapies, which can lead to substantially enhanced detrimental impacts on the malignant cells. The multifunctional GO‐based nanocomposites appear to be very promising for simultaneous imaging and therapy of cancer. For instance, the upconversion nanoparticles (UCNPs) coated with GO and quantum dot (GOQD) have been developed and used as image‐guided probes. In a study, to develop GO‐based multimodal NPs, core‐shell NPs composing of UCNP as a core and a GOQD as a shell were developed. For PDT, hypocrellin A (HA), as a chemotherapy and photo‐sensitizing agent, was conjugated onto the GOQD through a π−π interaction and loaded on the PEGylated UCNP. The engineered HA‐loaded GOQD‐UCNPs were proposed as a multifunctional NS for the simultaneous imaging and therapy of cancer [16]. In a similar study, a hybrid NS of GOQD was developed as a pH‐responsive fluorescent probe to serve as an improved cancer detection agent. The resulting biocompatible composites exhibited upconversion photoluminescence (UCPL) as well as fluorescence, at which the NS was proposed as a fluorescence/photoluminescence‐guided probe for the detection of cancer [17]. The pH‐responsive curcumin‐containing composites of GO/QD have also recently been developed and successfully used in vitro and in vivo for concurrent imaging and chemotherapy of cancer [18].

Some studies have shown an excellent NIR‐absorption ability and payload capacity for rGO. As a result, it might be selected as a delivery system to combine the PTT/PDT with chemotherapy for improved treatment against different types of cancers. For example, in a study, rGO was loaded with doxorubicin (DOX) and chlorin e6 as a photosensitizer, which was then used against cancer in vitro and in vivo. The therapeutic efficacies of graphene‐based NSs were studied in combination with PDT, PTT, and chemotherapy on 2D/3D cultured tumor cells (spheroid/tumoroid) and animal models with results showing the efficacy of nanomedicine‐based PTT compared to chemotherapy and PDT modalities in cancer treatment [19]. Further, in an interesting research, GO was reduced by glucose to develop the glucose‐functionalized biocompatible rGO for PTT of the LNCaP prostate cancer cells. Results suggested that the biocompatible GO/glucose NS could be efficiently used for PTT of cancer [20]. A large number of investigations have been conducted using different types of nucleic acids for targeted gene therapy of cancers. However, the main issue in the gene therapy is the lack of suitable gene delivery system, in large part due to immunogenicity of the viral vectors and genotoxicity of nonviral vectors [21–26]. GO‐based NSs can provide a suitable platform for the delivery genes (see Figure 11.3). [28, 29]. For instance, the GO functionalized with hyaluronic acid (HA), to serve as a fluorescence‐switchable theranostic nanoplatform, was fabricated for simultaneous sensing of miR‐21 and inhibiting its tumorigenicity in vitro and in vivo. The Cy3‐labeled antisense miR‐21 peptide nucleic acid (PNA) probes loaded onto the HA‐GO (HGP21) were shown to specifically target the CD44‐positive MBA‐MB231 cells, in which a fluorescence recovery was observed through an interaction with the cytoplasmic miR‐21. In the miR‐21 knockdown mice induced by HGP21, decreased proliferation and migration of cancer cells with induction of apoptosis and enhanced phosphatase and tensin homolog located on chromosome ten (PTEN) levels were reported. Furthermore, in vivo imaging in the tumor‐bearing mice showed fluorescence signals three hours after the IV injection of the NS, upon which the researchers proposed it as a multifunctional theranostic for the miRNA‐targeted diagnosis/therapy [30]

11.2.2 Polymeric Graphene Nanocomposites

Polymeric NCs have been developed using various types of NPs (e.g. magnetic, gold, and graphene NPs), and widely used for the cancer therapy. However, occurrence of systemic cytotoxicity together with the inherent poor‐solubility of these NSs have often limited their biological applications. Polymeric nanohybrids can be harnessed to improve the biocompatibility and multi‐responsiveness of DDSs in the cancer therapy.

In a study, magnetic graphene nanosheets (MGNs) were engineered, coated with Pluronic F127 (PF127) and loaded with DOX. The resultant NS was used for the diagnosis and therapy of cancer simultaneously through the NIR‐mediated PTT in combination with chemotherapy, while displaying MRI potential [48]. Similarly, in another study, the iron oxide‐graphene NCs, stabilized by polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) (PVA) polymers, were loaded with paclitaxel (PTX) and DOX to treat the human cervical cancer HeLa cells. This NC showed a good loading capacity with a pH‐responsive release of DOX molecules and high efficiency. Once under the magnetic field, the NS showed excellent potential for imaging as well as synergistic PTT and chemotherapy effects. It should be noted that arming graphene sheets with PVP was shown to produce a pH‐trigged nanocarrier for delivery of anticancer agents (e.g. DOX). The cytotoxic effects of such NS have been evaluated on various cells lines, including HeLa, NIH‐3T3, HCT‐116, and 9HEK‐293 cells and SCC. The results revealed that the NS can impose profound cytotoxicity in the cancer cells [49].

Surface‐modified GO polymeric NSs were shown to serve as targeted DDS for PDT [50]. In this line, Huang et al. have developed PVP‐coated GO nanocomposites decorated with ACDCRGDCFCG peptide anchoring sites and loaded with chlorin e6 (Ce6) photosensitizer. The resulting targeted NS was found to improve the PDT by increasing the accumulation of Ce6 in tumor cells [51]. In an interesting study, Dou et al. developed NCs composed of rGO decorated bismuth sulfide (Bi₂S₃). The NCs were further functionalized with PVP and loaded with DOX, and successfully used for the chemophotothermal therapy of cancer. In fact, this dual NIR‐and pH‐responsive NS showed great effectiveness both in vitro and in vivo. Various cancer cells (BEL‐7402, MCF‐7, Hela, and HepG2 cells) and the human hepatoma (BEL‐7402) tumor‐bearing mice were treated with the NS and then irradiated by the NIR ray. The results showed marked synergistic antitumor effects inhibiting the growth of cancer. Besides, due to the X‐ray and NIR absorption capability of the engineered NS, it was proposed to be employed for the image‐guided synergistic chemophotothermal treatment of cancer [52]. Robinson et al. reported on the development of PEGylated rGO functionalized with RGD (Arg‐Gly‐Asp peptide) motif as a homing agent to selectively target the U87MG cancer cells. On the basis of in vitro biological stability and effective photoablation of the nano‐rGO in the presence of NIR irradiation, the researchers suggested it as a promising candidate for the NIR‐mediated PTT of cancer cells [53].

In a study, polymeric GNPs/GO theranostics were developed through a double‐microemulsion of GNPs into poly(lactic acid) microcapsules. The surface was further modified with GO through the electrostatic deposition technique. As shown in Figure 11.4, the engineered micro‐composite was developed to serve as a prognostic contrast agent in the simultaneous ultrasound/CT imaging in combination with PTT for multimodal image‐guided cancer therapy [54].

Recently, a chitosan (CS)‐based biodegradable hydrogel, consisting of polyethyleneimine (PEI) modified GO/MNP, was developed and loaded with DOX. The hydrogel was used as a minimally invasive system for the treatment of cancer lesions through magnetically induced local hyperthermia. Both in vitro and in vivo results revealed profound antitumor impacts of the hydrogel in the cancer cells and tumor tissue in the presence of magnetic field, at which it was introduced as a system with the synergetic effects of hyperthermia and chemotherapy [55]. Similarly, a versatile drug delivery NS based on functionalized GO with carboxymethyl chitosan (CMCS) was engineered to combine the PTT with chemotherapy using DOX. The modified biocompatible GO composites displayed pH‐responsive release behavior and effectively induced cell death in the liver cancer SMMC‐7721 cells [56]. In another investigation, to produce a pH‐sensitive carrier, surface‐carboxylated mesoporous silica‐coated magnetic GO modified with the CS polymer (i.e. by electrostatic interaction) and loaded with DOX was developed. The nanocarrier showed an improved stability and solubility in biological environments with a pH‐triggered release of DOX. As a result, the engineered NS was proposed as a potential candidate for the cancer therapy [57].

In a recent study, using electrospinning techniques, pH‐responsive GO/CS/polyethylene oxide (PEO) nanofibers loaded with DOX were developed and successfully used for the treatment of lung cancer. These nanofibers showed an excellent drug loading efficacy with a pH‐dependent release of cargo drug [58]. Some reports have clearly highlighted that the routine clinical treatments (chemotherapy, radiotherapy, and surgical resection) of brain cancer are very aggressive approaches with a high mortality rate. To tackle this issue, Su et al. reported on the development of an alternative noninvasive PTT for brain tumors using porphyrin functionalized GO. The in vitro findings revealed marked ablation of the malignant cells with specific targeted PTT [9]. Surface modification of graphene and its derivatives is considered as an effective strategy to improve their solubility that is associated with their cytotoxicity effects. To investigate the impacts of GO nanocomposites in the cancer therapy, Liu et al. developed silica and GO core/shell NSs. To enhance the stability and solubility of the NCs, they were conjugated to the serum proteins and used as an advanced DDS to deliver DOX to the cervical cancer cells. The in vitro analyses confirmed markedly higher cytotoxicity induced by the NSs under irradiation with NIR laser. In addition, the tumor growth in animal models treated with the NS was substantially inhibited in the presence of the NIR irradiation, indicating its impacts as a PTT agent [59].

By far, a variety of graphene‐based magnetic nanocomposites have been engineered to serve as a chemophotothermal therapy agent, which can be used as magnetic‐field‐assisted DDS. In this line, to elicit chemophotothermal synergistic impacts on the HeLa cancer cells using magnetic‐field‐assisted DDS, Chen et al. capitalized on PEGylated MNPs/Au core‐shell nanoparticles modified with rGO and loaded with DOX. These researchers showed that the DOX‐loaded NS could induce synergistic chemotherapeutic impacts on the cells through magnetic‐field‐guided delivery of drug combined with PTT [60]. Likewise, in another study, the Ag/GO nanocomposites loaded with DOX and functionalized with DSPE‐PEG2000‐Asn‐Gly‐Arg (nitrogen‐doped graphene (NGR)) motif were developed. This multimodal NS, as a NIR‐controlled drug delivery nanohybrid, was used for active targeting of the breast cancer. The in vitro experiments confirmed the ability of the engineered NS in terms of NIR‐mediated drug release and chemo‐photothermal therapy. Further, the in vivo biodistribution and the X‐ray imaging studies confirmed the potential of Ag/GO‐DOX‐NGR nanosystems for the simultaneous diagnosis and therapy of cancer [61].

It should be highlighted that the incidences of inevitable unwanted side effects of chemotherapy, which can lead to failure of chemotherapy, have accelerated researches towards the development of multimodal targeted NSs. To mitigate adverse reactions of the conventional chemotherapies, GO hybridized alginate nanogels were fabricated and encapsulated with DOX, which was used to treat the lung cancer A549 cells. The NS was shown to be markedly internalized by the cancer cells, resulting in an enhanced anticancer activity as a multimodal nanomedicine [62]. In another attempt, surface functionalized GO with poly(dopamine) was used for the encapsulation of cytarabine hydrochloride as a chemophotothermal therapy agent. Both in vitro analysis in the HeLa cells and in vivo animal studies of the NS confirmed its biocompatibility, sustained‐release profile, responsiveness to the NIR laser, and the synergistic chemotherapeutic efficiency (under 808 nm NIR laser) and significantly suppressing of tumor growth, indicating great therapeutic efficacy of this versatile nanohybrid [63].

In an attempt to improve the stability and biocompatibility of graphene‐based drug delivery vehicles, FITC‐functionalized poly(N‐isopropylacrylamide) (PNIPAM) grafted GO was developed and encapsulated with indomethacin (IMC) and DOX. The engineered NS showed a pH‐responsive release pattern for both IMC and DOX and a great ability for the fluorescence imaging of cancerous cells [64]. Further, it should be pointed out that the polymeric NSs of GO and thermo‐responsive nanogels (NGs) based on the NIPAM and acrylic acid have previously been developed as nanoscaled stimuli‐responsive (e.g. pH and temperature) DDS [65]. Such nanoporous structures can be used for the encapsulation of anticancer agents (e.g. DOX, PX, MTX) to treat solid tumors such as the cervical cancer. These nanocomposites exhibited sustained‐release pattern at the lower temperatures and the neutral pH. However, drug release was significantly accelerated at the higher temperatures and the acidic pH. Such dual‐mediated release by both temperature and pH appeared to enhance the cytotoxicity associated with the drug‐loaded NS, at which they were proposed as dual‐stimuli responsive NS for delivery of anticancer agents into the target cancer cells [65]. In an interesting experiment, pH‐sensitiveGO‐based nanovehicles were developed through functionalization of GO with 2,3‐dimethylmaleic anhydride and modification with poly(allylamine hydrochloride) and polyethylene glycol (PEG). The NS was loaded with DOX and used to serve as an anticancer agent. The NS showed an improved toxicity in the cancer cells, in large part because of the pH‐mediated release of the drug in the tumor microenvironment. In addition, the photothermal conversion ability of nanohybrid was found to enhance the therapeutic effectivity in the cancer cells [66].

11.3 Multimodal Graphene‐Based Composites for the Radiotherapy of Cancer

The growing interest in effective bioimaging and targeted therapy of tumor cells/tissue is one of the main goals among scientists worldwide. Recently, several studies have been carried out to incorporate diagnostic/therapeutic radioisotopes with NSs that are able to induce combined PTT/PDT effects, and hence to be used as theranostics. Owing to an optimal biocompatibility and low cytotoxicity of GO and its composites, they have a great capacity to serve as multimodal radiolabeled theranostics. Recently, PEGylated nano rGO (nRGO‐PEG) was reported to serve as in vivo PTT nanoprobe in the 4T1 murine breast cancer cells−bearing mice. The biodistribution and tumor accumulation studies of the NS were performed using ¹²⁵ I‐labeled NSs in the animal models. The developed rGO‐PEG exhibited strong NIR absorption capacity with passive targeting mechanism in solid tumors. Furthermore, rGO‐PEG presented efficient tumor ablation after an intravenous injection in the presence of a low laser power density. Such compelling findings suggested that both the size and the surface chemistry of nanomaterials could impose critical effects on the in vivo behaviors of GO nanocomposites and their potential in PPT of cancer [75]. In a similar study, to develop a nuclear image‐guided probe to combine the PTT with radiotherapy, the PEGlyted rGO was radiolabeled with ¹³¹ I (¹³¹ I‐rGO‐PEG) and used as a radiopharmaceutical against cancer cells. The in vivo gamma imaging illustrated marked accumulation of ¹³¹ I‐rGO‐PEG in the tumor sites after an intravenous injection. Furthermore, this NS was shown to induce an enhanced PTT effect in the presence of NIR light irradiation and an emission of the ionizing high‐energy X‐ray (by ¹³¹ I) simultaneously [76]. In another study, to target and diagnose cancer cells, Song et al. developed hybrid GNR/rGO nanocomposites loaded with DOX and radiolabeled with ⁶⁴ Cu. The NS was successfully used for simultaneous in vivo PET imaging and chemophotothermal therapy in the presence of NIR in the U87MG tumor‐bearing animals. The nanocomposites showed high accumulation in the TME through passive targeting mechanism and strong photoacoustic trait in the tumor site. The use of this NS resulted in a significant inhibition in the tumor growth, in large part because of the synergistic effects of chemophotothermal therapy [77].

Taken together, the GO offers unique characteristics, including (i) physicochemical properties (e.g. biocompatibility, high surface area, thermal conductivity, and photoacoustic trait), (ii) remarkable advancements in biomedical applications, and (iii) in vivo impacts (i.e. GO‐based theranostics) on cancer cells. Thus, it is envisioned that they have great potential for translation into the clinical applications. Among many different attempts for biomedical cancer diagnosis/therapy, in a study, GO was functionalized with monoclonal antibody (mAb) specific to the follicle‐stimulating hormone receptor (FSHR) and radiolabeled with ⁶⁴ Cu for targeted PET imaging of the angiogenic biomarkers and therapy. This multimodal NS was used to track the angiogenesis during breast cancer progression and metastasis. The in vitro and in vivo studies on the breast cancer cell line and animal model showed great targeting potential and efficacy (Figure 11.5). As a result, the NS was proposed to serve as multimodal theranostic for simultaneous early diagnosis and targeted therapy [78].

In another interesting investigation, the GO/Fe₃O₄@SiO₂ nanocomposite was radiolabeled with Rhenium‐188 (¹⁸⁸ Re‐ GO/Fe₃O₄@SiO₂) and loaded with gambogic acid (GA). The NS was introduced as a multifunctional theranostic and successfully used for magnetic drug delivery and radionuclide therapy in VX‐2‐bearing nude mice. While the release of the GA was shown to be pH‐responsive, the in vivo biodistribution of the NSs was found to be dependent on their morphology. The peanut‐like nanocomposites were found to be accumulated in the lung, spleen, and liver more than the spherical ones, and could markedly inhibit the tumor cell growth as compared to the nontargeted therapy [79].

11.4 Graphene‐Based Nanobiomaterials for Cancer Diagnosis

Given the remarkable photoacoustic and surface functionalization potentials of graphene and its derivatives, they are considered as promising materials for the detection and monitoring of solid tumors. By far, several studies have been carried out to implement different strategies to enhance and improve the photoconversion efficiency of such advanced nanobiomaterials to serve as probes for the early detection of cancer biomarkers in biological fluids of patients. To benefit such potentials, in a study, nanocomposites of GO/GNPs were developed to amplify signals in the surface Plasmon resonance (SPR)‐based detection of micro RNAs involved in the development and progression of cancer. In this study, the thiolated DNAs were immobilized on the gold surface to identify the target miRNAs. The engineered GO/GNPs provided great potential for quantitative early detection of miRNAs (miRNA‐200) with a limit of detection (LOD) as low as 1 fM [80]. In a similar attempt, GO/GNPs nanohybrids were designed for the analysis of miRNA‐141. The fabricated SPR‐based biosensor exhibited exceptional selectivity and sensitivity for the detection of different biomolecules such as miRNA‐141 with a LOD of 0.1 fM [81]. In a study, the nanohybrid of functionalized graphene with polyamidoamine and Ag nanoparticles were developed as a substrate to the sensitive surface‐enhanced Raman spectroscopy for the detection of methimazole (MTZ). This graphene‐based nanohybrid was found to enhance the bands of MTZ with an increased detection sensitivity to a picomolar range [82]. In fact, an exact analysis of biomolecules at a very low level is an important strategy, particularly when their amounts are extremely low. For example, in the blood, the circulating tumor cells (CTCs) and exosomes are very low. Therefore, their selective separation and identification among billions of biological entities in the blood appear to be an enormously complex issue. To tackle such a hurdle, Shi et al. decorated the GO/quantum dots (QDs) with MNPs and conjugated them with anti‐glypican‐3(GPC3) antibody. The NS was proposed to serve as a luminescent agent and successfully used for the two‐photon imaging at 960 nm light in a biological transparency range. The engineered NSs were effectively used for the separation of GPC3‐expressing HepG2 hepatocellular carcinoma tumor CTCs from the blood [83].

11.5 Conclusion

In this chapter, we summarized the recent advancements in engineering and application of the graphene‐based nanomaterials used for the development of multifunctional nanomedicines and theranostics. Owing to the photoacoustic properties of the graphene‐based nanomaterials, they include imaging and PTT/PDT potentials to multifunctional NSs providing great simultaneous imaging and synergistic therapy impacts on the cancer cells. Further, these advanced materials can be used in the development of different types of nanobiosensors to serve as nanoprobes for the detection of extremely low amounts of biological entities such as cancer markers and CTCs. In addition, combination therapy using graphene and its derivatives have widely been extended, resulting in the production of new generation of multimodal pharmaceuticals. In this regard, the ability of graphene nanocomposites as the NIR‐absorbing agents provides great opportunity in terms of variant light‐to‐heat conversion and NIR‐mediated PTT/PDT. These modalities and other image‐guided therapies of cancer through graphene‐based multimodal nanomedicines/theranostics make them outstanding materials that can be functionalized with different types of inorganic and/or organic materials, resulting in hybrid stimuli‐responsive NSs. These seamless NSs offer simultaneous targeting, imaging, and therapy potentials, and many of these NSs are under clinical translation. Despite many advancements, the paramount challenges in the translation of the multifunctional GO graphene‐based structures for imaging and targeted therapy seem to be the development of graphene‐based NSs with high in vivo stability, immune responsibility, and trivial/no toxicity.

Acknowledgment

The authors would like to acknowledge the financial support received from the Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences.

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