Mengxin Zhang

Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly(lactic-co-glycolic acid) nanofibrous mats.

Currently, combining biomaterial scaffolds with living stem cells for tissue regeneration is a main approach for tissue engineering. Mesenchymal stem cells (MSCs) are promising candidates for musculoskeletal tissue repair through differentiating into specific tissues, such as bone, muscle, and cartilage. Thus, successfully directing the fate of MSCs through factors and inducers would improve regeneration efficiency. Here, we report the fabrication of graphene oxide (GO)-doped poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds via electrospinning technique for the enhancement of osteogenic differentiation of MSCs. GO-PLGA nanofibrous mats with three-dimensional porous structure and smooth surface can be readily produced via an electrospinning technique. GO plays two roles in the nanofibrous mats: first, it enhances the hydrophilic performance, and protein- and inducer-adsorption ability of the nanofibers. Second, the incorporated GO accelerates the human MSCs (hMSCs) adhesion and proliferation versus pure PLGA nanofiber and induces the osteogenic differentiation. The incorporating GO scaffold materials may find applications in tissue engineering and other fields.

Graphene Oxide Based Theranostic Platform for T1-Weighted Magnetic Resonance Imaging and Drug Delivery

Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the quality of MRI-based diagnosis. In this work, we developed a positive T1 MRI CA based on graphene oxide (GO)-gadolinium (Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO, followed by Gd(III) complexation, to form a T1 MRI CA (GO-DTPA-Gd). We have demonstrated that the GO-DTPA-Gd system significantly improves MRI T1 relaxivity and leads to a better cellular MRI contrast effect than Magnevist, a commercially used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface of GO sheets via physisorption. Thus-prepared GO-DTPA-Gd/DOX shows significant cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to build a GO-based theranostic nanoplatform with T1-weighted MRI, fluorescence imaging, and drug delivery functionalities.

Silicon Phthalocyanine Covalently Functionalized N-Doped Ultrasmall Reduced Graphene Oxide Decorated with Pt Nanoparticles for Hydrogen Evolution from Water

To improve the photocatalytic activity of graphene-based catalysts, silicon phthalocyanine (SiPc) covalently functionalized N-doped ultrasmall reduced graphene oxide (N-usRGO) has been synthesized through 1,3-dipolar cycloaddition of azomethine ylides. The obtained product (N-usRGO/SiPc) was characterized by transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, Raman spectra, X-ray photoelectron spectroscopy, fluorescence, and UV-vis spectroscopy. The results demonstrate that SiPc has been successfully grafted on the surface of N-usRGO. The N-usRGO/SiPc nanocomposite exhibits high light-harvesting efficiency covering a range of wavelengths from the ultraviolet to visible light. The efficient fluorescence quenching and the enhanced photocurrent response confirm that the photoinduced electron transfers from the SiPc moiety to the N-usRGO sheet. Moreover, we chose Pt nanoparticles as cocatalyst to load on N-usRGO/SiPc sheets to obtain the optimal H2 production effect. The platinized N-usRGO/SiPc (N-usRGO/SiPc/Pt) demonstrates good hydrogen evolution performance under both UV-vis and visible light (λ>400 nm) irradiation. The apparent quantum yields are 1.3% and 0.56% at 365 and 420 nm, respectively. These results reveal that N-usRGO/SiPc/Pt nanocomposite, consolidating the advantages of SiPc, N-usRGO, and Pt NPs, can be a potential candidate for hydrogen evolution from water under UV-vis or visible light irradiation.

Manganese doped iron oxide theranostic nanoparticles for combined T1 magnetic resonance imaging and photothermal therapy.

Photothermal therapy (PTT) is a noninvasive and convenient way to ablate tumor tissues. Integrating PTT with imaging technique could precisely identify the location and the size of tumor regions, thereby significantly improving the therapeutic efficacy. Magnetic resonance imaging (MRI) is widely used in clinical diagnosis due to its superb spatial resolution and real-time monitoring feature. In our work, we developed a theranostic nanoplatform based on manganese doped iron oxide (MnIO) nanoparticles modified with denatured bovine serum albumin (MnIO-dBSA). The in vitro experiment revealed that the MnIO nanoparticles exhibited T1-weighted MRI capability (r1 = 8.24 mM(-1) s(-1), r2/r1 = 2.18) and good photothermal effect under near-infrared laser irradiation (808 nm). Using 4T1 tumor-bearing mice as an animal model, we further demonstrated that the MnIO-dBSA composites could significantly increase T1 MRI signal intensity at the tumor site (about two times) and effectively ablate tumor tissues with photoirradiation. Taken together, this work demonstrates the great potential of the MnIO nanoparticles as an ideal theranostic platform for efficient tumor MR imaging and photothermal therapy.

PEGylated carbon nanoparticles for efficient in vitro photothermal cancer therapy

Photothermal therapy (PTT) is an emerging technique for effective cancer elimination in animal experiments. The key to the success of the PTT is to develop efficient and safe photosensitive agents. Activated carbon (AC), a widespread material safely used in routine and emergent medical services, is emerging as a nascent PTT agent. Here we report for the first time synthesis and in vitro PTT application of carbon nanoparticles (CNPs, less than 10 nm) derived from AC. In our strategy, CNPs are obtained via chemical oxidation and transferred to PEGylated CNPs (PCNPs) to reduce nonspecific adsorption and to improve biocompatibility. Fluorescein isothiocyanate is conjugated to PCNPs to examine time-dependent uptake by human breast cancer cells (MCF-7). The photothermal effect experiment demonstrates that PCNPs possess much stronger photothermal conversion ability than carbon dots (CDs). In the dark, PCNPs pose negligible threats to cell viability and membrane integrity, while upon near infrared (NIR) irradiation PCNPs can effectively kill cancer cells. The current work demonstrates that PCNPs can be used as an efficient and safe PTT agent.

Removal and recycling of ppm levels of methylene blue from an aqueous solution with graphene oxide

Dye-containing wastewater is one of the major issues in water contamination, and its treatment remains a serious problem due to the low concentrations of dyes in polluted natural water and high cost for purification. Herein, we report the application of graphene oxides (GO) in the decontamination of ppm levels of methylene blue (MB) in an aqueous solution. During the dye removal process, GO adsorbs MB molecules via strong interactions including π–π stacking and electrostatic attraction, and facilitates the precipitation of GO/MB complexes, which can be readily removed from the solution. The adsorption progress follows the Langmuir isotherm model and the pseudo-second-order kinetic model. The thermodynamic parameters indicate that the adsorption progress is a spontaneous progress. By using our strategy, a dye removal rate as high as 95% has been achieved with a final dye concentration of only 0.25 ppm. In addition, 82% of the dye can be recycled through ethanol extraction from the collected GO/MB complexes. All the results demonstrate that GO nanosheets can effectively remove and recover ppm levels of cationic dye pollutants, represented by MB, showing the promising application of GO in ultra-low concentration dye containing wastewater treatment.

Combination of TNF-α and graphene oxide-loaded BEZ235 to enhance apoptosis of PIK3CA mutant colorectal cancer cells

The PI3K-AKT-mTOR pathway plays an important role in tumor cell growth, invasion, migration and apoptosis. A blockade of this signaling pathway has arisen as a compelling target for the tumor therapy. However, there is cross-talking between different signal pathways. Combined treatment of tumors with different signal pathway inhibitors is considered as an efficient strategy for cancer therapy. NVP-BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor currently in clinical trial. TNF-α is involved in the regulation of cell apoptosis. In the current work, we explored the combined use of BEZ235 and TNF-α on the PIK3CA mutant colorectal cancer (CRC) cell proliferation inhibition. In our strategy, the BEZ235 is loaded on PEGylated graphene oxide (GO-PEG) by physisorption viaπ-π stacking to enhance its aqueous solubility. The resulting GO-BEZ235 complex exhibited excellent aqueous solubility while retaining a high cancer cell killing potency. The combination of BEZ235 and TNF-α shows an enhanced cellular proliferation inhibition for HCT 116 through enhancing the G1 phase arrest and cell apoptosis compared to either drug alone. Moreover, our experiments reveal that the enhanced tumor cell apoptosis depends on the activation of caspase-9, caspase-8 and caspase-3 mediated by the increased phosphorylation level of JNK. Taken together, our findings demonstrate for the first time the feasibility of BEZ235 delivered by GO-PEG and of the combined use of BEZ235 and TNF-α for PIK3CA mutant CRC therapy.

Facile-synthesized ultrasmall CuS nanocrystals as drug nanocarriers for highly effective chemo–photothermal combination therapy of cancer

Combinational chemo–photothermal therapy has been considered as a promising strategy to enhance antitumor efficiency via synergistic effects for cancer treatments. Here, we have developed a smart ‘all-in-one’ platform that conveniently combined chemo- and photothermal therapies based on ultrasmall CuS NCs, which were synthesized using a facile, low cost, and water solution reaction method. Doxorubicin (Dox)-loaded CuS drug nanocarriers (CuS–Dox) were fabricated with loading capacity up to 21%. The resulting CuS–Dox exhibited pH and NIR light dual-responsiveness, demonstrating remarkably promoted Dox release in a weakly acidic environment in cancer cells and enhanced intercellular uptake under 808 nm laser irradiation. Based on in vitro cell cytotoxicity, the CuS–Dox endow excellent chemo–photothermal synergistic effects for cancer cell death or apoptosis, attributed to both the cytotoxicity of light-triggered Dox release and CuS-mediated photothermal ablation. More importantly, in vivo treatment has achieved the complete inhibition of tumor growth in 4T1-bearing mice under a low laser power density of 1.0 W cm−2. These results demonstrate a better anti-tumor therapeutic efficacy of combined treatment in vitro and in vivo in comparison with chemotherapy or photothermal therapy alone. Our study highlights the promise of fabricating CuS–Dox drug nanocarriers for highly effective chemo–photothermal combination therapy of cancer.

Ultrasmall graphene oxide based T1 MRI contrast agent for in vitro and in vivo labeling of human mesenchymal stem cells

Herein, we report on development of a two-dimensional nanomaterial graphene oxide (GO)-based T1 magnetic resonance imaging (MRI) contrast agent (CA) for in vitro and in vivo labeling of human mesenchymal stem cells (hMSCs). The CA was synthesized by PEGylation of ultrasmall GO, followed by conjugation with a chelating agent DOTA and then gadolinium(III) to form GO-DOTA-Gd complexes. Thus-prepared GO-DOTA-Gd complexes exhibited significantly improved T1 relaxivity, and the r1 value was 14.2 mM-1s-1 at 11.7 T, approximately three times higher than Magnevist, a commercially available CA. hMSCs can be effectively labeled by GO-DOTA-Gd, leading to remarkably enhanced cellular MRI effect without obvious adverse effects on proliferation and differentiation of hMSCs. More importantly, in vivo experiment revealed that intracranial detection of 5×105 hMSCs labeled with GO-DOTA-Gd is achieved. The current work demonstrates the feasibility of the GO-based T1 MRI CA for stem cell labeling, which may find potential applications in regenerative medicine.

Graphene for Biomedical Applications

Graphene has attracted extensive attention in the field for biomedicine in recent years, due to its fine compatibility and extremely large surface area to accommodate a large amount of therapeutic agents, as well as the possibilities to serve for photothermal or photodynamic therapy on its own. In addition, its wide applications in biomedicine triggered massive investigations on its toxicity and biological activities as culturing substrates. In this chapter, we will survey the emerging applications of graphene and its related derivatives in the field of biology and medicine, including drug delivery, therapeutics, imaging and sensing, as well as cell culture substrates and antibacterial performance.