PEGylated Nanographene Oxide Research Articles

Celastrol Loaded PEGylated Nanographene Oxide for Highly Efficient Synergistic Chemo/Photothermal Therapy.

The main aim of this study is to improve the solubility, reduce side effects and increase the therapeutic efficacy of CSL by using functionalized graphene oxide as a carrier, to fulfill chemo-photothermal therapy. Celastrol (CSL), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has reported significant antitumor activity in vitro and in vivo cancer models. However, disadvantages with regard to solubility, short plasma half-life and toxicity hinder its use in pharmaceutical application. Nanocarrier delivery system could be employed to improve the biochemical and pharmacokinetic performance of CSL. Among numerous nanocarriers, graphene oxide is one of the most promising nanocarriers due to its intrinsic physical and chemical properties and good biocompatibility. Here, we employed a PEGylated reduced nanographene oxide CSL complex (nrGO-PEG/CSL) as a new drug delivery system to achieve highly efficient synergistic chemo/photothermal therapy. A functionalized nrGO-PEG was synthesized and the loading capacity of CSL, photothermal effect and release efficiency under different pH and NIR irradiation were measured in the first stage of work. In vitro and in vivo anticancer effects of prepared nrGO-PEG/CSL complex were evaluated on 4T1 cells and 4T1 tumor-bearing mice, respectively, with the association of NIR laser irradiation. The functionalized nrGO-PEG exhibited excellent drug loading capacity of CSL (20.76 mg/mg GO) and photothermal effect (~3.0 -fold increment over unreduced nGO-PEG). Loaded CSL could be efficiently released from nrGO-PEG/CSL complex by NIR irradiation in vitro. In vivo study performed on 4T1 tumor-bearing mice proved that nrGO-PEG/CSL with NIR laser irradiation shows superior anticancer effects. The experimental data demonstrated that the nrGO-PEG/CSL-mediated chemo/photothermal combination therapy was more cytotoxic to cancer cells than only chemotherapy or photothermal treatment, reducing the occurrence of tumor metastasis. Therefore, nrGO-PEG/CSL-mediated chemo/photothermal is expected to be a promising treatment for synergistic cancer therapy.

PEGylated Nanographene Oxide in Combination with Near-Infrared Laser Irradiation as a Smart Nanocarrier in Colon Cancer Targeted Therapy.

Anti-cancer therapies that integrate smart nanomaterials are the focus of cancer research in recent years. Here, we present our results with PEGylated nanographene oxide particles (nGO-PEG) and have studied their combined effect with near-infrared (NIR) irradiation on low and high invasive colorectal carcinoma cells. The aim is to develop nGO-PEG as a smart nanocarrier for colon cancer-targeted therapy. For this purpose, nGO-PEG nanoparticles’ size, zeta potential, surface morphology, dispersion stability, aggregation, and sterility were determined and compared with pristine nGO nanoparticles (NPs). Our results show that PEGylation increased the particle sizes from 256.7 nm (pristine nGO) to 324.6 nm (nGO-PEG), the zeta potential from −32.9 to −21.6 mV, and wrinkled the surface of the nanosheets. Furthermore, nGO-PEG exhibited higher absorbance in the NIR region, as compared to unmodified nGO. PEGylated nGO demonstrated enhanced stability in aqueous solution, improved dispensability in the culture medium, containing 10% fetal bovine serum (FBS) and amended biocompatibility. A strong synergic effect of nGO-PEG activated with NIR irradiation for 5 min (1.5 W/cm−2 laser) was observed on cell growth inhibition of low invasive colon cancer cells (HT29) and their wound closure ability while the effect of NIR on cellular morphology was relatively weak. Our results show that PEGylation of nGO combined with NIR irradiation holds the potential for a biocompatible smart nanocarrier in colon cancer cells with enhanced physicochemical properties and higher biological compatibility. For that reason, further optimization of the irradiation process and detailed screening of nGO-PEG in combination with NIR and chemotherapeutics on the fate of the colon cancer cells is a prerequisite for highly efficient combined nanothermal and photothermal therapy for colon cancer.

Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma

BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors.Methods and resultsBased on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells.ConclusionThe mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Preparation and Optimization of PEGylated Nano Graphene Oxide-Based Delivery System for Drugs with Different Molecular Structures Using Design of Experiment (DoE).

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm–1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).

Synthesis of PEGylated nanographene oxide as a nanocarrier for docetaxel drugs and anticancer activity on prostate cancer cell lines.

Graphene oxide (GO) has recently been considered one of the most promising carbon derivatives in nanotechnology. It has many excellent features such as tumor targeting ability, biocompatibility and low toxicity. Therefore, we conjugated docetaxel (DTX) to GO-PEG molecule and investigate its anticancer efficacy in prostate cancer cell line (DU-145). In order to obtain GO-PEG-DTX molecules, we conjugated the DTX via bonds to PEG chains pegylated to the GO surface. We also investigated the stability of GO-PEG-DTX in different biological fluids such as cell mediums, PBS and water in vitro conditions. GO-PEG-DTX has the highest zeta potential in water. In the current research SEM, UV-Vis, and FTIR analyses and zeta potential were utilized for the characterization of nano-sized GO-PEG-DTX. Anticancer efficacy of GO-PEG-DTX were then investigated in DU-145 prostate cancer cell line using MTT metod. The prostate cancer cells were treated by different concentrations of GO-PEG-DTX, GO-PEG, GO, and DTX (1-100 µg/ml) during 24, 48 and 72 h. The spectrophotometric analyzed values at 570 nm were recorded and analysed with Graphpad Prism7. IC50 growth inhibition values was determined. The data showed that the GO-PEG-DTX had a highly effective anticancer activity on prostate cancer cell lines after 24, 48 and 72 hours compared to other molecules. GO-PEG-DTX was found statistically significant in the DU-145 cell line (***p < 0.0001, **p < 0.001, and *p < 0.01). As a result, it can be said that PEGylated GO is an excellent nanocarrier system for the high anticancer activity of DTX. Loading of anticancer drugs using this type of graphene-based nano carrier and delivery to targeted tissues may find potential application in biomedicine.

Graphene oxide activated by 980 nm laser for cascading two-photon photodynamic therapy and photothermal therapy against breast cancer

Combinational applying photodynamic therapy (PDT) and photothermal therapy (PTT) have been extensively studied, while simultaneously exciting with a single wavelength NIR laser remains challenges. In this study, PEGylated nano graphene oxide co-loaded with photosensitizers (PS) and two-photon compound was developed as a theranostic nanomedicine GO-PEG(TP) against cancer. Two-photon compound could convert near-infrared laser into visible light for exciting PS thus achieved deeper therapeutic depth. The size, morphology and drug release profile of GO-PEG(TP) were characterized. The photoactivity of PS and two-photon compound get quenched on the graphene sheet, whereas activated quickly after releasing from carrier. Such combined therapy shows blasting of 4T1 murine breast cancer cells and induced large population of apoptosis. Ex vivo distribution and in vivo thermographic images were analyzed by using GO-PEG(TP) as probe, on subcutaneously 4T1 tumor bearing mice. Combinational therapy and histology examination reveal the antitumor property and biosafety of GO-PEG(TP).

Aggregation-Induced Emission Nanoparticles Encapsulated with PEGylated Nano Graphene Oxide and Their Applications in Two-Photon Fluorescence Bioimaging and Photodynamic Therapy in Vitro and in Vivo.

Aggregation-induced emission (AIE) nanoparticles have been shown promise for fluorescence bioimaging and photodynamic therapy due to the good combination of nanoparticles and organic dyes or photosensitizers. Among several kinds of AIE nanoparticles, those that are capsulated with nanographene oxides (NGO) are easy to make, size-tunable, and have proven to be very stable in deionized water. However, the stability in saline solution still needs improvement for further applications in chemical or biomedical fields, and the efficacy of photodynamic therapy using NGO-capsulate AIE photosensitizers has not been evaluated yet. Herein, we modified NGO with polyethylene glycol (PEG) to improve the stability of NGO-capsulated AIE nanoparticles in phosphate buffer saline. Furthermore, by combining this modification methodwith a dual-functional moleculewhich has both typical AIE property and photosensitizing ability, we performed both two-photon fluorescence bioimaging and photodynamic therapy in vitro and in vivo. Our work shows that AIE nanoparticles capsulated with PEGylated nanographene oxide can be a powerful tool for future bioimaging and photodynamic therapy applications.

Chelator-Free Conjugation of 99mTc and Gd3+ to PEGylated Nanographene Oxide for Dual-Modality SPECT/MR Imaging of Lymph Nodes.

PEGylated ultrasmall nanographene oxide (usNGO-PEG) has exhibited a great potential in nanotheranostics due to its newly discovered physicochemical properties derived from the rich functional groups and bonds. Herein, we developed a general, simple, and kitlike preparation approach for 99mTc- and Gd-anchored NGO-PEG using a chelator-free strategy. In this strategy, [99mTcI(CO)3(OH2)3]+ (abbreviated to 99mTcI) and GdCl3 were mixed with usNGO-PEG to yield 99mTc- and Gd-usNGO-PEG via the synergistic coordination of N and O atoms from NGO and PEG with 99mTcI and Gd3+ without additional exogenous chelators. Under optimized conditions, the nanoprobes 99mTc- and Gd-usNGO-PEG were reliably prepared with high yields and good stability. Serial comparative experiments of the labeling yield, the measurements of -NH2 density and ζ-potentials, and various characterizations including energy-dispersive X-ray analysis spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy demonstrated that both usNGO and PEG synergistically provide the electron-donating atoms O and N to coordinate with 99mTcI and Gd to form stable nanocomplexes. Furthermore, both 99mTc- and Gd-usNGO-PEG exhibited excellent in vivo imaging of lymph nodes using single-photon emission computed tomography/computed tomography (SPECT/CT) and magnetic resonance (MR) imaging after local injection. Therefore, these results showed the successful establishment of 99mTc- and Gd-anchored usNGO-PEG using a chelator-free strategy and the potential of multimodality SPECT/CT and MR imaging of lymph nodes.

Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy.

Poor water-solubility of artesunate (ARS) hampers its clinical application. We here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen species (ROS) and peroxynitrite (ONOO─) generations. Although nGO-PEG with near-infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO─ generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO─ scavenger) instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation, demonstrating that ONOO─ instead of ROS dominated the synergistic chemo-photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation resulted in a complete tumor cure within 15 days earlier than other treatment groups, and did not induce apparent histological lesion for the mice treated with nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy.

Hydrothermal Reduction of Polyethylenimine and Polyethylene Glycol Dual-Functionalized Nanographene Oxide for High-Efficiency Gene Delivery.

In this study, a physiologically stable dual-polymer-functionalized reduced nanographene oxide (nrGO) conjugate (PEG-nrGO-PEI, RGPP) with high efficiency of gene delivery is successfully synthesized through mixing PEGylated nanographene oxide (PEG-nGO, GP) and polyethylenimine (PEI, 25 kDa) solution under 80 °C for 2 h. This hydrothermal reduction of GP during PEIylation promotes the nucleophilic reaction between the amino moieties of PEI and the epoxy groups (or carboxylic groups) in GP and then forms C-NH- groups (or NH-CO groups) to covalently connect PEI and GP, which makes the RGPP nanocomposite more stable in physiological environments and has superior gene transfection efficiency compared with the nonhydrothermally reduced PEG-nGO/PEI conjugate (GPP) obtained by mixing GP and PEI under 20 °C for 2 h. Moreover, 808 nm laser irradiation (2 W/cm2) for 25 min increases ∼1.5-fold of gene transfection efficiency for RGPP but does not increase the gene transfection efficiency of GPP. Finally, RGPP is also able to efficiently deliver functional plasmid GFP-Bax (pGFP-Bax), exhibiting ∼43% of transfection efficiency in HepG2 cells. Collectively, the RGPP developed here is a highly efficient nanocarrier for gene delivery, and this work encourages further explorations of developing functionalized reduced nano-GO for high-efficiency gene therapy.

Somatostatin Receptor-Mediated Tumor-Targeting Nanocarriers Based on Octreotide-PEG Conjugated Nanographene Oxide for Combined Chemo and Photothermal Therapy.

Nano-sized in vivo active targeting drug delivery systems have been developed to a high anti-tumor efficacy strategy against certain cancer-cells-specific. Graphene based nanocarriers with unique physical and chemical properties have shown significant potentials in this aspect. Here, octreotide (OCT), an efficient biotarget molecule, is conjugated to PEGylated nanographene oxide (NGO) drug carriers for the first time. The obtained NGO-PEG-OCT complex shows low toxicity and excellent stability in vivo and is able to achieve somatostatin receptor-mediated tumor-specific targeting delivery. Owing to the high loading efficiency and accurate targeting delivery of anti-cancer drug doxorubicin (DOX), our DOX loaded NGO-PEG-OCT complex offers a remarkably improved cancer-cell-specific cellular uptake, chemo-cytotoxicity, and decreased systemic toxicity compared to free DOX or NGO-PEG. More importantly, due to its strong near-infrared absorption, the NGO-PEG-OCT complex further enhances efficient photothermal ablation of tumors, delivering combined chemo and photothermal therapeutic effect against cancer cells.

One-step reduction and PEIylation of PEGylated nanographene oxide for highly efficient chemo-photothermal therapy.

Graphene oxide (GO) has great potential in biomedical applications due to its excellent photothermal effect and drug loading. Herein, dual-functionalized reduced nano-GO (nrGO-PEG/PEI) has been developed as a synergistic system of drug delivery and an NIR-light-absorbing agent. Covalently PEGylated nanographene oxide (nGO-PEG) was simultaneously reduced and PEIylated by bathing with polyethylenimine (PEI 1.8 kDa) solution in water at 80 °C for 2 h to obtain nrGO-PEG/PEI. nrGO-PEG/PEI exhibited low cytotoxicity and excellent dispersibility in physiological environments. Furthermore, nrGO-PEG/PEI had ∼20-fold increment in NIR absorption at 808 nm and ∼2.7-fold increment in doxorubicin (DOX) loading over unreduced nGO-PEG. Loaded DOX could be efficiently released from nrGO-PEG/PEI/DOX in an acidic environment (pH 5.0) and by NIR irradiation. In addition, nrGO-PEG/PEI could be rapidly encapsulated into cells and targeted to the nucleus region. In vitro and in vivo studies demonstrated the remarkable anticancer effects of nrGO-PEG/PEI/DOX with NIR laser irradiation. These results suggest that nrGO-PEG/PEI may be a novel drug delivery platform for controlling chemo-photothermal synergistic cancer therapy.

Visualization of size-dependent tumour retention of PEGylated nanographene oxide via SPECT imaging.

PEGylated nanosized graphene oxides (NGO-PEG) and related derivatives have attracted extensive attention owing to their unique properties, which confer significant theranostic benefits for cancer treatment. The size of NGO-PEG varies largely, from tens of nanometers to micrometers, and the optimal size range with the most efficient tumor retention in vivo remains to be determined. For this purpose, we designed different sizes of NGO-PEG, specifically, ultra-small NGO-PEG (usNGO-PEG, sub-50 nm) and NGO-PEG (over 50 nm) and compared their biological behaviors in vitro and in vivo. Both NGO-PEGs exhibited nearly identical physicochemical properties and low cytotoxicity. Following Cy5.5 tagging, confocal microscopy fluorescence imaging revealed faster and higher dynamic cellular uptake of usNGO-PEG than NGO-PEG. Longitudinal, non-invasive visualization of the NGO-PEGs using single proton emission computed tomography (SPECT) imaging with 125I-radiolabeling revealed that tumor retention of usNGO-PEG was significantly higher and longer compared to that of NGO-PEG, whereas the blood circulation and biodistribution of both NGO-PEGs were similar in major organs. In conclusion, Sub-50 nm was further confirmed to be the favorable size for efficient tumor accumulation of PEGylated GO via the enhanced permeability and retention (EPR) effect. We propose that the sub-50 nm NGO-PEG designed in this study may be effectively utilized to develop novel PEGylated GO-based nanoplatforms for multifunctional cancer nanotheranostics.

A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug

Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment.

Redox-responsive biodegradable PEGylated nanographene oxide for efficiently chemo-photothermal therapy: A comparative study with non-biodegradable PEGylated nanographene oxide

Nanographene oxide (NGO) with a non-sheddable poly(ethylene glycol) (PEG) coating has been used for chemo-photothermal therapy. However, the drug release of PEGylated NGO (NGO-PEG) with an amine bond is adversely affected by the diffusion barrier effect of PEG shells. Here, we developed a simple new method for the preparation of biodegradable PEGylated NGO conjugates (NGO-SS-PEG) with cleavable disulfide bonds for rapid drug release and more efficiently chemo-photothermal therapy. The glutathione (GSH)-induced and photothermal-mediated intracellular release of doxorubicin (DOX) from NGO-SS-PEG was studied in A549 cells using confocal laser scanning microscopy and flow cytometry analysis. In vivo cytotoxicity experiments were performed on chemo-photothermal therapy. Furthermore, we presented a comparative study of intracellular drug release and biological efficacy between NGO-SS-PEG/DOX and NGO-PEG/DOX. The results demonstrated that the rapid drug release from the NGO-SS-PEG conjugates with sheddable PEG was triggered upon the stimulus of high GSH levels inside A549 cells. Interesting, the DOX release mediated by the photothermal effect from the NGO-SS-PEG conjugates was found to be more obvious than that for NGO-PEG. Additionally, NGO-SS-PEG showed a higher efficacy than NGO-PEG for anti-tumor therapy compared with NGO-PEG. Thus, NGO-SS-PEG can improve therapeutic efficacy and is an attractive drug nanocarrier.

Facile and green reduction of covalently PEGylated nanographene oxide via a ‘water-only’ route for high-efficiency photothermal therapy

A facile and green strategy is reported for the fabrication of nanosized and reduced covalently PEGylated graphene oxide (nrGO-PEG) with great biocompatibility and high near-infrared (NIR) absorbance. Covalently PEGylated nGO (nGO-PEG) was synthesized by the reaction of nGO-COOH and methoxypolyethylene glycol amine (mPEG-NH2). The neutral and purified nGO-PEG solution was then directly bathed in water at 90°C for 24 h without any additive to obtain nrGO-PEG. Covalent PEGylation not only prevented the aggregation of nGO but also dramatically promoted the reduction extent of nGO during this reduction process. The resulting single-layered nrGO-PEG sheets were approximately 50 nm in average lateral dimension and exhibited great biocompatibility and approximately 7.6-fold increment in NIR absorption. Moreover, this facile reduction process repaired the aromatic structure of GO. CCK-8 and flow cytometry (FCM) assays showed that exposure of A549 cells to 100 μg/mL of nrGO-PEG for 2 h, exhibiting 71.5% of uptake ratio, did not induce significant cytotoxicity. However, after irradiation with 808 nm laser (0.6 W/cm2) for 5 min, the cells incubated with 6 μg/mL of nrGO-PEG solution showed approximately 90% decrease of cell viability, demonstrating the high-efficiency photothermal therapy of nrGO-PEG to tumor cells in vitro. This work established nrGO-PEG as a promising photothermal agent due to its small size, great biocompatibility, high photothermal efficiency, and low cost.

EGRF conjugated PEGylated nanographene oxide for targeted chemotherapy and photothermal therapy

Low accumulation of chemotherapeutic agent in tumor tissue and multidrug resistance (MDR) present a major obstacle to curing cancer treatment. Therefore, how to combine several therapeutics in one system is a key issue to overcome the problem. Here, we demonstrate epidermal growth factor receptor (EGFR) antibody-conjugated PEGylated nanographene oxide (PEG-NGO) to carry epirubicin (EPI) for tumor targeting and triple-therapeutics (growth signal blocking, chemotherapy, photothermal therapy) in tumor treatment. This synergistic targeted treatment simultaneously enhances the local drug concentration (6.3-fold) and performs the ultra-efficient tumor suppression to significantly prolong the mice survival (over the course of 50 days).

Cell uptake survey of pegylated nanographene oxide

Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml−1 pegylated GO solutions. GO uptake kinetics revealed differences in the agent’s uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide

Graphene has shown great potential both in photothermal therapy and drug delivery. Herein, we developed doxorubicin-loaded PEGylated nanographene oxide (NGO-PEG-DOX) to facilitate combined chemotherapy and photothermal therapy in one system. In this work, we studied the ablation of tumor both in vivo and in vitro by the combination of photothermal therapy and chemotherapy using this functional graphene oxide. The ability of the NGO-PEG-DOX nanoparticle to combine the local specific chemotherapy with external near-infrared (NIR) photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy. Furthermore, lower systematic toxicity of NGO-PEG-DOX than DOX was proved by the pathologic examination of main organs in our toxicity study.

PEGylated nanographene oxide for delivery of water-insoluble cancer drugs.

It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.