Optimizing the nanostructure of graphene oxide/silver/arginine for effective wound healing.

In this study, we introduce a novel graphene oxide/silver/arginine (GO/Ag/Arg) nanohybrid structure, which can act as an angiogenesis promoter and provide antibacterial nanostructure for improving the wound healing process. GO/Ag nanostructure has been optimized in terms of the GO/Ag mass ratio and pH values using central composite design and the response surface method to increase the Ag loading efficiency. Then, Arg was chemically introduced to the surface of GO/Ag nanostructure. Electrospun polycaprolactone (PCL)-GO/Ag/Arg nanocomposite was successfully fabricated and characterized. The synthesized nanocomposite demonstrated not only a great antibacterial effect on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial species, but appropriate biocompatibility against L929 fibroblastic cell lines. The results demonstrated that the preparation of the PCL-GO/Ag/Arg nanocomposite at a concentration of 1.0 wt% GO/Ag/Arg possessed the best biological and mechanical features. In vivo experiments also revealed that the use of optimized PCL-GO/Ag/Arg nanocomposite, after 12 d of treatment, led to significant increase in the healing process and also regeneration of the wound via reconstruction of a thickened epidermis layer on the wound surface, which was confirmed by histological analysis. In conclusion, the proposed approach can introduce a novel notion for preparing antibacterial material that significantly promotes angiogenesis.

Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading.

Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers.

Theranostic applications of stimulus-responsive systems based on carbon dots.

Over recent years, many different nanoparticle-based drug delivery systems (NDDSs) have been developed. Recently the development of stimulus-responsive NDDSs has come into sharper focus. Carbon dots (CDs) possess outstanding features such as useful optical properties, good biocompatibility, and the ability for easy surface modification. Appropriate surface modification can allow these NDDSs to respond to various chemical or physical stimuli that are characteristic of their target cells or tissue (frequently malignant cells or tumors). The present review covers recent developments of CDs in NDDSs with a particular focus on internal stimulus response capability that allows simultaneous imaging and therapeutic delivery (theranostics). Relevant stimuli associated with tumor cells and tumors include pH levels, redox potential, and different enzymatic activities can be used to activate the CDs at the desired sites.

Microfluidic synthesis of PLGA/carbon quantum dot microspheres for vascular endothelial growth factor delivery.

In this study, vascular endothelial growth factor (VEGF) loaded poly(d,l-lactide-co-glycolide) (PLGA) - carbon quantum dot microspheres were produced using microfluidic platforms. The microcapsules were fabricated in flow-focusing geometry with a biphasic flow to generate solid/oil/water (s-o-w) droplets. To avoid any damage to protein functional and structural stability during the encapsulation process, the VEGF was PEGylated. The produced microspheres were intact and highly monodisperse in size (CV < 5%). Furthermore, microspheres in a size range of 16-36 µm were achieved by adjusting the flow ratio parameter. The encapsulation efficiency, release profile, and bioactivity of the produced microparticles were also studied. The loading efficiency of PEGylated VEGF in the microparticles was varied from 51-69% and more than 90% of PEGylated VEGF was released within 28 days. Furthermore, the release of VEGF was indirectly monitored by carbon quantum dots. The present monodisperse and controllable VEGF loaded microspheres with reproducible manner could be widely used in tissue engineering and therapeutic applications.

An electrochemical biosensor for prostate cancer biomarker detection using graphene oxide-gold nanostructures.

In this paper, a most sensitive electrochemical biosensor for detection of prostate-specific antigen (PSA) was designed. To reach the goal, a sandwich type electrode composed of reduced graphene oxide/ gold nanoparticles (GO/AuNPs), Anti-Total PSA monoclonal antibody, and anti-Free PSA antibody was assembled. The functionalized materials were thoroughly characterized by atomic force microscope spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. The electrochemical properties of each of the modification step were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The results presented that the proposed biosensor possesses high sensitivity toward total and free PSA. Furthermore, the fabricated biosensor revealed an excellent selectivity for PSA in comparison to the other tumor markers such as BHCG, Alb, CEA, CA125, and CA19-9. The limit of detection for the proposed electrochemical biosensor was estimated to be around 0.2 and 0.07 ng/mL for total and free PSA antigen, respectively.

Self-assembling of graphene oxide on carbon quantum dot loaded liposomes.

This paper describes the design of stimuli-sensitive theranostic nanoparticles, composed of reduced graphene oxide (rGO) self-assembled on thermosensitive liposomes encapsulated doxorubicin (DOX) and carbon quantum dot (CQD) (CQD-DOX-rGO-Tlip). The rGO-Tlip particles have been observed to be flower-shaped objects. The thermoresponsive and theranostic potential of CQD-DOX-rGO-Tlips have been studied using differential scanning calorimetry (DSC), ultraviolet visible spectroscopy (UV-Vis), Raman spectroscopy and photoluminescent assays. The chemo-photothermal potential of rGO-Tlip on MD-MB-231 cells during NIR laser irradiation has been examined using MTT assay. Also, the ability of rGO-Tlip to be taken up by MD-MB-231 cells has been studied using confocal microscopy and flowcytometry. The results indicate that CQD-DOX-rGO-Tlips achieve a synergistic effect between photothermal therapy and chemotherapy for cancer treatment. Furthermore, online monitoring drug release is accomplished by studying the emission intensity of CQD while DOX released.

Effect of size and chemical composition of graphene oxide nanoparticles on optical absorption cross-section.

Photothermal therapy with various nanoparticles, as photothermal transducers, is a widely researched technique. A continuous wave (CW) laser is employed during this procedure. The therapeutic setup is slightly modified to measure the optical absorption cross-section of the graphene oxide (GO), by mitigating the effects of heat diffusion and light scattering. With an 808-nm CW laser setup modulated by a waveform modulation setup, the effect of nanoparticle size and composition of GO in water on optical absorption cross section is characterized.

Layer-by-layer assembly of graphene oxide on thermosensitive liposomes for photo-chemotherapy.

Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited on cationic liposomes encapsulating doxorubicin. Various concentrations of GO and GO-PLL were examined and the optimal LBL Lipo-graph was found to have a particle size of 267.9 ±â€¯13 nm, zeta potential of +43.9 ±â€¯6.9 mV and encapsulation efficiency of 86.4 ±â€¯4.7%. The morphology of LBL Lipo-graph was examined by cryogenic-transmission electron microscopy (Cryo-TEM), atomic force microcopy (AFM) and scanning electron microscopy (SEM). The buildup of LBL Lipo-graph was confirmed via ultraviolet-visible (UV-Vis) spectrophotometry, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis. Infra-red (IR) response suggests that four layers are sufficient to induce a gel-to-liquid phase transition in response to near infra-red (NIR) laser irradiation. Light-matter interaction of LBL Lipo-graph was studied by calculating the absorption cross section in the frequency domain by utilizing Fourier analysis. Drug release assay indicates that the LBL Lipo-graph releases much faster in an acidic environment than a liposome control. A cytotoxicity assay was conducted to prove the efficacy of LBL Lipo-graph to destroy MD-MB-231 cells in response to NIR laser emission. Also, image stream flow cytometry and two photon microcopy provide supportive data for the potential application of LBL Lipo-graph for photothermal therapy. Study results suggest the novel dual-sensitive nanoparticles allow intracellular doxorubin delivery and respond to either acidic environments or NIR excitation. STATEMENT OF SIGNIFICANCE: Stimuli sensitive hybrid nanoparticles have been synthesized using a layer-by-layer technique and demonstrated for dual chemo-photothermal destruction of breast cancer cells. The hybrid nanoparticles are composed of alternating layers of graphene oxide and graphene oxide conjugated poly-l-lysine coating the surface of a thermosensitive cationic liposome containing doxorubicin as a core. Data suggests that the hybrid nanoparticles may offer many advantages for chemo-photothermal therapy. Advantages include a decrease of the initial burst release which may result in the reduction in systemic toxicity, increase in pH responsivity around the tumor environment and improved NIR light absorption.

Evaluation of the Photothermal Properties of a Reduced Graphene Oxide/Arginine Nanostructure for Near-Infrared Absorption.

Strong near-infrared (NIR) absorption of reduced graphene oxide (rGO) make this material a candidate for photothermal therapy. The use of rGO has been limited by low stability in aqueous media due to the lack of surface hydrophilic groups. We report synthesis of a novel form of reduced graphene-arginine (rGO-Arg) as a nanoprobe. Introduction of Arg to the surface of rGO not only increases the stability in aqueous solutions but also increases cancer cell uptake. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) images are recorded to characterize the morphology of rGO-Arg. Fourier transform infrared (FTIR), X-ray photoelectron spectra (XPS), Raman, and UV-vis spectroscopy are utilized to analyze the physiochemical properties of rGO-Arg. Interaction of rGO-Arg with 808 nm laser light has been evaluated by measuring the absorption cross section in response to periodically modulated intensity to minimize artifacts arising from lateral thermal diffusion with a material scattering matched to a low scattering optical standard. Cell toxicity and cellular uptake by MD-MB-231 cell lines provide supporting data for the potential application of rGO-Arg for photothermal therapy. Absorption cross-section results suggest rGO-Arg is an excellent NIR absorber that is 3.2 times stronger in comparison to GO.