Graphene-silymarin-loaded chitosan/gelatin/hyaluronic acid hybrid constructs for advanced full-thickness burn wound management.

Burn wounds (BWs) with extensive blood loss, along with bacterial infections and poor healing, may become detrimental and pose significant rehabilitation obstacles in medical facilities. Therefore, the freeze-drying method synthesized novel hemocompatible chitosan, gelatin, and hyaluronic acid infused with graphene oxide-silymarin (CGH-SGO) hybrid constructs for application as a BW patch. Most significantly, synthesized hybrid constructs exhibited an interconnected-porous framework with precise pore sizes (≈118.52 µm) conducive to biological functions. Furthermore, the FTIR and XRD analyses document the constructs' physiochemical interactions. Similarly, enhanced swelling ratios, adequate WVTR (736 ± 78 g m-2 hr-1), and bio-degradation rates were seen during the physiological examination of constructs. Following the in vitro investigations, SMN-GO added to constructs improved their anti-bacterial (against E.coli and S. aureus), anti-oxidant, hemocompatible, and bio-compatible characteristics in conjunction with prolonged drug release. Furthermore, in vivo, implanting constructs on wounds exhibited significant acceleration in full-thickness burn wound (FT-BW) healing on the 14th day (CGH-SGO: 95 ± 2.1 %) in contrast with the control (Gauze: 71 ± 4.2 %). Additionally, contrary to gauze, the in vivo rat tail excision model administered with constructs assured immediate blood clotting. Therefore, CGH-SGO constructs with an improved porous framework, anti-bacterial activity, hemocompatibility, and biocompatibility could represent an attractive option for healing FT-BWs.

Plasmonic laser-responsive BioDissolve 3D-printed graphene@cisplatin-implant for prevention of post-surgical relapse of oral cancer.

The development of chemoresistance is a major obstacle in post-surgical adjuvant therapy of cancer, leading to cancer cell survival, recurrence, and metastasis. This study reports a 3D-printed plasmonic implant developed for the post-surgical adjuvant therapy of cisplatin-resistant cancer cells to prevent relapse. The implant was printed using optimized biomaterial ink containing biodegradable polymers [poly(L-lactide) and hydroxypropyl methylcellulose] blended suitably with laser-responsive graphene and chemo drug (Cisplatin). The irradiation of scar-driven 3D-printed implant with a laser stimulates graphene to generate a series of hyperthermia events leading to photothermolysis of cisplatin-resistant cancer cells under the combined influence of sustained cisplatin release. The developed personalized implant offers pH-responsive sustained drug release for 28 days. The implant exhibited acceptable biophysical properties (Tensile strength: 3.99 ± 0.15 MPa; modulus: 81 ± 9.58 MPa; thickness: 110 µm). The 3D-printed implant effectively reverses the chemoresistance in cisplatin-resistant 3D spheroid tumor models. Cytotoxicity assay performed using cisplatin-resistant (CisR) cell line revealed that the cell viability was reduced to 39.80 ± 0.68 % from 61.37 ± 0.98 % in CisR tumor spheroids on combined chemo-photothermal therapy. The combination therapy reduced the IC50 value from 71.05 µM to 48.73 µM in CisR spheroids. Apoptosis assay revealed an increase in the population of apoptotic cells (35.45 ± 1.56 % →52.53 ± 2.30 %) on combination therapy. A similar trend was observed in gene expression analysis, where the expression of pro-apoptotic genes Caspase 3 (3.73 ± 0.04 fold) and Bcl-2-associated X protein (BAX) (3.35 ± 0.02 fold) was increased on combination therapy. This 3D-printed, biodegradable implant with chemo-combined thermal ablating potential may provide a promising approach for the adjuvant treatment of resistant cancer.

Synthesis of a novel ternary ZIF-8/GO/MgFe2O4 nanocomposite and its application in drug delivery.

In recent year, metal-organic frameworks (MOFs) have been displayed to be a category of promising drug delivery systems because of their crystalline structure, the potential of further functionality, and high porosity. In this research, graphene oxide was synthesized from pure graphite via hummer method and then MgFe2O4 nanoparticles was incorporated into the synthesized ZIF-8 metal-organic frameworks which followed with loading on the surfaces of graphene oxide. In continue, tetracycline as an antibiotic drug was loaded on the surfaces and the cavities of the prepared nanocomposite. The outcomes of this research revealed that 90% of the tetracycline was loaded on the synthesized ZIF-8/GO/MgFe2O4 nanostructure. Next, drug release was done at pH: 5 and pH: 7.4 within 3 days, resulting about 88% and 92% release of the tetracycline, respectively. With using different spectroscopic methods like X-ray crystallography (XRD), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX/Mapping), Fourier transform infrared (FTIR), thermalgravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET), the structure of synthesized materials was confirmed. Furthermore, the antibiotic activity of tetracycline trapped into the ZIF-8/GO/MgFe2O4 was evaluated by agar-well diffusion method on both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria, which showed good antibacterial results.

Acute administration of sulfur-doped g-C3N4 induces cognitive deficits and exacerbates the levels of glial activation in mouse hippocampus.

During the last decades, graphitic carbon nitride (g-C3N4) has attracted increasing attention in several biomedical fields. In this study, the effects of sulfur-doped g-C3N4 (TCN) on cognitive function and histopathology of hippocampus were investigated in mice. The characteristics of synthetized sample were evaluated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray (EDX). Twenty-four male NMRI mice received vehicle, TCN at doses of 50, 150, or 500 mg/kg via gavage for one week. Morris water maze test was done to assess the cognitive function at day 14 post TCN administration. Nissl staining was used to determine the number of dark cells in the hippocampus. Immunostaining against NeuN, GFAP, and Iba1 was done to evaluate the neuronal density and levels of glial activation, respectively. Behavioral tests indicated that TCN reduces the spatial learning and memory in a dose-dependent manner. Histological evaluations showed an increased level of neuronal loss and glial activation in the hippocampus of TCN treated mice at doses of 150 and 500 mg/kg. Overall, our data indicate that TCN induces the cognitive impairment that is partly mediated via its exacerbating impacts on neuronal loss and glial activation.

Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application.

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75-90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide-polyethylene glycol (GOP)-PCA/CA-FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP-PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.

Lidocaine-loaded reduced graphene oxide hydrogel for prolongation of effects of local anesthesia: In vitro and in vivo analyses.

Lidocaine is widely used as a local anesthetic for alleviation of post-operative pain and for management of acute and chronic painful conditions. Although several approaches are currently used to prolong the duration of action, an effective strategy to achieve neural blockage for several hours remains to be identified. In this study, a lidocaine-loaded Pluronic® F68-reduced graphene oxide hydrogel was developed to achieve sustained release of lidocaine. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic® F68-reduced graphene oxide. Transmission electron microscopy showed wrinkled, flat nanosheets with micelles attached. The developed hydrogel showed desirable pH, viscosity, adhesiveness, hardness, and cohesiveness for topical application. The ex vivo release study demonstrated the ability of the Pluronic® F68-reduced graphene oxide hydrogel to prolong release up to 10 h, owing to the strong π-π interactions between the graphene oxide and the lidocaine. In comparison with a commercial lidocaine ointment, the developed graphene oxide hydrogel showed sustained anesthetic effect in the radiant heat tail flick test and sciatic nerve block model. Thus, this study demonstrates the potential of using Pluronic® F68-reduced graphene oxide nanocarriers to realize prolonged effects of local anesthesia for effective pain management.

Graphene oxide loaded with tumor-targeted peptide and anti-cancer drugs for cancer target therapy.

In the present work, we constructed nanoscale graphene oxide (NGO) as a drug nanocarrier to improve the process of tumor-targeted drug releases, promote cellular uptake and accumulation of chemotherapy drugs in tumor tissues, and reduce the toxic effects of chemotherapy drugs on normal cells. Hence, great stability was obtained in the biological solution. Moreover, we designed an effective nanoparticle system for the doxorubicin (DOX) delivery targeting the oral squamous cell carcinoma (OSCC) by mediating the HN-1 (TSPLNIHNGQKL) through hydrogen and π-π bonds. DOX@NGO-PEG-HN-1 showed significantly higher cellular uptakes and cytotoxicity in OSCC cells (CAL-27 and SCC-25), compared to free DOX. Moreover, HN-1 showed considerable tumor-targeting and competition inhibition phenomenon. As we expected, the nanocarrier showed pH-responsive drug release. In total, our study represented a good technique to construct OSCC-targeted delivery of nanoparticles and improve the anticancer medicines' efficiency.

Occupational exposure to graphene and silica nanoparticles. Part II: pilot study to identify a panel of sensitive biomarkers of genotoxic, oxidative and inflammatory effects on suitable biological matrices.

The available biomonitoring studies on workers producing/handling nanomaterials (NMs) focused on potential effects on respiratory, immune and cardio-vascular system. Aim of this study was to identify a panel of sensitive biomarkers and suitable biological matrices to evaluate particularly genotoxic and oxidative effects induced on workers unintentionally exposed to graphene or silica nanoparticles during the production process. These nanomaterials have been chosen for 'NanoKey' project, integrating the workplace exposure assessment (reported in part I) with the biomonitoring of exposed workers reported in the present work. Simultaneously to workplace exposure characterization, we monitored the workers using: Buccal Micronucleus Cytome (BMCyt) assay, fpg-comet test (lymphocytes), oxidized DNA bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo measurements (urine), analysis of oxidative stress biomarkers in exhaled breath condensate (EBC), FENO measurement and cytokines release detection (serum). Since buccal cells are among the main targets of NM occupational exposure, particular attention was posed to the BMCyt assay that represents a noninvasive assay. This pilot study, performed on 12 workers vs.11 controls, demonstrates that BMCyt and fpg-comet assays are the most sensitive biomarkers of early, still reparable, genotoxic and oxidative effects. The findings suggest that these biomarkers could represent useful tools for the biomonitoring of workers exposed to nanoparticles, but they need to be confirmed on a high number of subjects. However, such biomarkers don't discriminate the effects of NM from those due to other chemicals used in the NM production process. Therefore, they could be suitable for the biomonitoring of workers exposed to complex scenario, including nanoparticles exposure.

A transcriptomic overview of lung and liver changes one day after pulmonary exposure to graphene and graphene oxide.

Hazard evaluation of graphene-based materials (GBM) is still in its early stage and it is slowed by their large diversity in the physicochemical properties. This study explores transcriptomic differences in the lung and liver after pulmonary exposure to two GBM with similar physical properties, but different surface chemistry. Female C57BL/6 mice were exposed by a single intratracheal instillation of 0, 18, 54 or 162 µg/mouse of graphene oxide (GO) or reduced graphene oxide (rGO). Pulmonary and hepatic changes in the transcriptome were profiled to identify commonly and uniquely perturbed functions and pathways by GO and rGO. These changes were then related to previously analyzed toxicity endpoints. GO exposure induced more differentially expressed genes, affected more functions, and perturbed more pathways compared to rGO, both in lung and liver tissues. The largest differences were observed for the pulmonary innate immune response and acute phase response, and for hepatic lipid homeostasis, which were strongly induced after GO exposure. These changes collective indicate a potential for atherosclerotic changes after GO, but not rGO exposure. As GO and rGO are physically similar, the higher level of hydroxyl groups on the surface of GO is likely the main reason for the observed differences. GO exposure also uniquely induced changes in the transcriptome related to fibrosis, whereas both GBM induced similar changes related to Reactive Oxygen Species production and genotoxicity. The differences in transcriptomic responses between the two GBM types can be used to understand how physicochemical properties influence biological responses and enable hazard evaluation of GBM and hazard ranking of GO and rGO, both in relation to each other and to other nanomaterials.

Influence of the Aspect Ratio of Iron Oxide Nanorods on Hysteresis-Loss-Mediated Magnetic Hyperthermia.

Owing to the problems associated with conventional cancer treatment methods, magnetic hyperthermia-based cancer therapy has gained importance recently. Achieving the desired heating effect at the site of the tumor with a minimal concentration of iron oxide nanoparticles (IONPs) and a safer field is necessary to explore the advantages of hyperthermia. For one to address this challenge, biocompatible IONPs with a desirable magnetic response at a tolerable field are necessary. In this work, magnetic shape anisotropy of iron oxide nanorods (NR) of different lengths (70, 115, 170, and 210 nm) with different aspect ratios ranging from 1.55 to 3.2 was explored to achieve higher hysteresis loss, in turn leading to better hyperthermia efficiency. The magnetic properties of the NRs with respect to the applied field were studied using micromagnetic simulation. Even though the nanorods with high aspect ratio showed a higher hysteresis loss of 69485 J/m3 at 2000 Oe, the field required to attain it was high and well beyond the safety limit. From nanorods of various aspect ratios, the nanorod with a lower aspect ratio of 1.55 and a length of 70 nm exhibited a better hysteresis loss and specific absorption rate (SAR) value of 4214 W g-1 was achieved at a frequency and alternating magnetic field of 400 kHz and 800 Oe, respectively. The PEGylated GO-Nanorod of 70 nm exhibited excellent antitumor efficacy in 4T1 tumor model mice by obstructing the tumor progression within a safer dosage and field.

Graphene oxide improves postoperative cognitive dysfunction by maximally alleviating amyloid beta burden in mice.

Rationale: Graphene oxide (GO) based nanomaterials have shown potential for the diagnosis and treatment of amyloid-ß (Aß)-related diseases, mainly on Alzheimer's disease (AD). However, these nanomaterials have limitations. How GO is beneficial to eliminate Aß burden, and its physiological function in Aß-related diseases, still needs to be investigated. Moreover, postoperative cognitive dysfunction (POCD) is an Aß-related common central nervous system complication, however, nanomedicine treatment is lacking. Methods: To evaluate the effects of GO on Aß levels, HEK293T-APP-GFP and SHSY5Y-APP-GFP cells are established. Intramedullary fixation surgery for tibial fractures under inhalation anesthesia is used to induce dysfunction of fear memory in mice. The fear memory of mice is assessed by fear conditioning test. Results: GO treatment maximally alleviated Aß levels by simultaneously reducing Aß generation and enhancing its degradation through inhibiting ß-cleavage of amyloid precursor protein (APP) and improving endosomal Aß delivery to lysosomes, respectively. In postoperative mice, the hippocampal Aß levels were significantly increased and hippocampal-dependent fear memory was impaired. However, GO administration significantly reduced hippocampal Aß levels and improved the cognitive function of the postoperative mice. Conclusion: GO improves fear memory of postoperative mice by maximally alleviating Aß accumulation, providing new evidence for the application of GO-based nanomedicines in Aß-related diseases.

Enhanced antitumor activity of bovine lactoferrin through immobilization onto functionalized nano graphene oxide: an in vitro/in vivo study.

This study aims to improve the anticancer activity of bovine lactoferrin through enhancing its stability by immobilization onto graphene oxide. Bovine lactoferrin was conjugated onto graphene oxide and the conjugation process was confirmed by FT-IR, SDS-PAGE, and UV spectrophotometry. Physical characterization was performed by DLS analysis and atomic force microscopy. The cytotoxicity and cellular uptake of the final construct (CGO-PEG-bLF) was inspected on lung cancer TC-1 cells by MTT assay and flow cytometry/confocal microscopy. The anticancer mechanism of the CGO-PEG-bLF was studied by cell cycle analysis, apoptosis assay, and western blot technique. Finally, the anticancer activity of CGO-PEG-bLF was assessed in an animal model of lung cancer. Size and zeta potential of CGO-PEG-bLF was obtained in the optimum range. Compared with free bLF, more cytotoxic activity, cellular uptake and more survival time was obtained for CGO-PEG-bLF. CGO-PEG-bLF significantly inhibited tumor growth in the animal model. Cell cycle arrest and apoptosis were more induced by CGO-PEG-bLF. Moreover, exposure to CGO-PEG-bLF decreased the phospho-AKT and pro-Caspase 3 levels and increased the amount of cleaved caspase 3 in the treated cells. This study revealed the potential of CGO-PEG as a promising nanocarrier for enhancing the therapeutic efficacy of anticancer agents.

Biodistribution of Graphene Oxide Determined through Postadministration Labeling with DNA-Conjugated Gold Nanoparticles and ICPMS.

Recent research has revealed the use of graphene oxide (GO) and its derivatives as a potential biomaterial because of their attractive physicochemical characteristics and functional properties. However, if GO and related derivatives are to become useful materials for biomedical applications, it will be necessary to evaluate their biodistribution for health and safety considerations. To obtain a more accurate biodistribution for GO, we (i) developed a postadministration labeling strategy employing DNA-conjugated gold nanoparticles (DNA-AuNPs) to selectively label administered GO in Solvable-treated tissue samples and (ii) constructed an automatic sample pretreatment scheme (using a C18-packed minicolumn) to effectively separate the DNA-AuNP-labeled GO from the unbound DNA-AuNPs and the dissolved tissue matrices, thereby enabling ultrasensitive, interference-free quantification of GO through measurement (inductively coupled plasma mass spectrometry) of the Au signal intensities. The DNA-AuNPs can bind to GO in a concentration- and time-dependent manner. After optimizing the labeling conditions (DNA length, incubation pH, DNA-AuNP concentration, and incubation time) and the separation scheme (sample loading flow rate, rinsing volume, and eluent composition), we found that A20R20-AuNPs (R20: random DNA sequence including A, T, C, and G) had the strongest binding affinity for labeling of the administered GO (dissociation constant: 36.0 fM) and that the method's detection limit reached 9.3 ag L-1 with a calibration curve having a working range from 10-1 to 1010 fg L-1. Moreover, this approach revealed that the intravenously administered GO accumulated predominantly in the liver and spleen at 1 and 12 h post administration, with apparent discrepancies in the concentrations measured using pre- and postadministration labeling strategies.

Molecular targeting of bioconjugated graphene oxide nanocarriers revealed at a cellular level using label-free Raman imaging.

Two-dimensional materials as graphene oxide (GO) are able to accommodate labels as well as toxins for diagnostics and therapy, respectively. The transmembrane protein carbonic anhydrase (CA IX) is one of the molecules selectively expressed by tumor cells. Here, we demonstrate bioconjugation of GO to biotinylated M75 antibody highly selective towards CA IX. Based on a model system, binding between the bioconjugated GO-M75 and Madin-Darby Canine Kidney (MDCK) cells was evaluated. As proven by fluorescence-activated cell sorting, higher intake was observed for GO-M75 towards MDCK cells ectopically expressing CA IX protein on their surface when compared to control MDCK. In particular, we were able to localize GO nanocarrier crossing the membrane during endocytosis, thanks to the optical cross-sectioning of living cells in real-time employed the label-free confocal Raman microscopy. The increased affinity of the prepared GO-M75 molecular complexes validates the use of two-dimensional materials for future strategies of targeted cancer treatment.

Implant-based direction of magnetic nanoporous silica nanoparticles - influence of macrophage depletion and infection.

Implant associated infections are still key problem in surgery. In the present study, the combination of a magnetic implant with administered magnetic nanoporous silica nanoparticles as potential drug carriers was examined in mice in dependence of local infection and macrophages as influencing factors. Four groups of mice (with and without implant infection and with and without macrophage depletion) received a magnet on the left and a titanium control on the right hind leg. Then, fluorescent nanoparticles were administered and particle accumulations at implant surfaces and in inner organs as well as local tissue reactions were analyzed. Magnetic nanoparticles could be found at the surfaces of magnetic implants in different amounts depending on the treatment groups and only rarely at titanium surfaces. Different interactions of magnetic implants, particles, infection and surrounding tissues occurred. The general principle of targeted accumulation of magnetic nanoparticles could be proven.

Electrospun poly-caprolactone/graphene oxide/quercetin nanofibrous scaffold for wound dressing: Evaluation of biological and structural properties.

AIMS: In this study, for the first time, the effect of quercetin (Q) on the characteristic properties, antimicrobial activity, and cell viability of polycaprolactone (PCL)/graphene oxide (GO) electrospun scaffold was investigated. MAIN METHODS: Quercetin loaded graphene oxide nanoparticles have been incorporated into the poly-caprolactone solution, and their mixture has been electrospun to be applied as a nanofibrous scaffold for wound dressing and tissue engineering applications. The properties of scaffolds, like their morphology, tensile strength, hydrophilicity, and in vitro biological performance, are investigated. KEY FINDINGS: The SEM micrographs reveal the uniform bead-free nanofibers with smooth structures have been successfully fabricated via the electrospinning procedure. The overall average of cell viability of NIH/3 T3 fibroblast cells on scaffolds is 95% that means the scaffolds have no toxicity, and FESEM shows cells attach and proliferate on scaffolds. Moreover, among all the fabricated scaffolds, the maximum release of quercetin belongs to PCL/GO/Q 0.5 with about 70% after 15 days, and this scaffold reduces bacterial growth by about 50% after 12 h shows the excellent effect of GO/Q on the antibacterial activity of PCL nanofibers. SIGNIFICANCE: The results confirm that more than 1% of GO has some cytotoxicity, which limits its concentration; therefore, a second antibacterial agent is essential to improve the antibacterial activity of PCL/GO scaffold, and quercetin shows that it is an excellent candidate for this purpose.

Reduced graphene oxide mitigates cadmium-induced cytotoxicity and oxidative stress in HepG2 cells.

Numerous applications of reduced graphene oxide (RGO) and pervasive cadmium (Cd) have led concern about their co-exposure to the environment and human. We studied the combined effects of RGO and Cd in human liver (HepG2) cells. Initially, we found that RGO (up to 50 µg/ml) did not harm to HepG2 cells while Cd induced dose-dependent (1-10 µg/ml) cytotoxicity. Exciting observations were that a non-cytotoxic concentration of RGO (25 µg/ml) effectively mitigates the toxic effects of Cd (2 µg/ml) such as cell viability reduction, lactate dehydrogenase release, and irregular cell morphology. Cd-induced cell cycle arrest, induction of caspases (3 and 9) enzymes activity, and loss of mitochondrial membrane potential were also significantly alleviated by RGO co-exposure. Moreover, generation of pro-oxidants (reactive oxygen species and hydrogen peroxide levels) and depletion of antioxidants (glutathione level and superoxide dismutase activity) due to Cd exposure was effectively attenuated by RGO co-exposure. Mitigating effect of RGO could be due to strong adsorption of Cd on the large surface area of RGO sheets, which decrease the cellular uptake and bioavailability of Cd for HepG2 cells. This study warrants future research on potential mechanisms of mitigating effects of RGO against Cd-induced toxicity in animal models.

Liposomal nanotheranostics for multimode targeted in vivo bioimaging and near-infrared light mediated cancer therapy.

Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and emissive graphene quantum dots (GQDs) were engineered named as NFGL. Further, doxorubicin hydrochloride was encapsulated in NFGL to exhibit phototriggered chemotherapy and functionalized with folic acid targeting ligands. Encapsulated agents showed imaging bimodality for in vivo tumor diagnosis due to their high contrast and emissive nature. Targeted NFGL nanohybrids demonstrated near infrared light (NIR, 750 nm) mediated tumor reduction because of generated heat and Reactive Oxygen Species (ROS). Moreover, NFGL nanohybrids exhibited remarkable ROS scavenging ability as compared to GQDs loaded liposomes validated by antitumor study. Hence, this approach and engineered system could open new direction for targeted imaging and cancer therapy.

Optically controlled hybrid metamaterial of plasmonic spiky gold inbuilt graphene sheets for bimodal imaging guided multimodal therapy.

The development of multifunctional molecular diagnostic platforms for the concordant visualization and treatment of diseases with high sensitivity and resolution has recently become a crucial strategy in cancer management. Thus, engineering functional metamaterials with high therapeutic and imaging capabilities to elucidate diseases from their morphological behaviors to physiological mechanisms is an unmet need in the current scenario. Here, we report the design of a unique hybrid plasmonic nanoarchitecture for targeted multiple phototherapies of breast cancer by simultaneous real-time monitoring through fluorescence and surface-enhanced Raman scattering (SERS) techniques. The nanoframework consisted of plasmonic gold-graphene hybrids tethered with folic acid-ligated chitosan-modified photosensitizer (PpIX) to afford target-specific localized photothermal and photodynamic therapy. The hybrid vehicle also served as an excellent nanocarrier for the efficient loading and stimuli-responsive release of the chemotherapeutic drug doxorubicin (DOX) to enhance the therapeutic efficacy, thereby forming a trimodal nanomedicine against cancer. The cytotoxic effects induced by the cumulative action of the triplet therapeutic tools were visualized through both fluorescence and SERS imaging channels. Moreover, it also generated synchronized therapeutic effects resulting in the effective regression of tumor volume without propagating any toxic effects to other organs of the animals. Taken together, by virtue of strong light-matter interactions, the nanoprobe showed enhanced photoadsorption, which facilitated amplified light-reactive therapeutic and imaging efficacies along with targeted and enhanced chemotherapy, both in vitro and in vivo, which may offer promising outcomes in clinical research.

In vivo immunological response of exposure to PEGylated graphene oxide via intraperitoneal injection.

Polyethylene glycol functionalization is believed to have the capacity of endowing nanomaterials with stealth characteristics, which can diminish the arrest by macrophages and adverse immunological response. However, our previous study provided evidences that polyethylene glycol-functionalized graphene oxide (GOP) stimulated a strong immunological response to macrophages despite non-internalization in vitro, raising safety concerns and potential immunostimulation use of GOP. In light of this finding, we herein systematically study the in vivo immunological response upon the exposure to GOP via intraperitoneal injection. Taking cytokines production, cell types in the peritoneal fluid, biochemical index, hematology and histopathology as in vivo indicators, we demonstrate that GOP still remains the stealth-but-activating capacity on macrophages in a time and dose-dependent manner. Specifically, the immune response can be significantly elevated after a single high-dose injection, indicating that GOP can be a new candidate adjuvant for immunotherapy. For multiple low dose injections, the immune response is gentle, temporary, and tolerable, which manifests the biocompatibility of GOP in general drug delivery. The above results can thus provide guidance for safe and rational use of GOP for various biomedical applications.