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1.
Int J Nanomedicine ; 19: 3957-3972, 2024.
Article En | MEDLINE | ID: mdl-38711614

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.


Copper , Doxorubicin , Graphite , Metal-Organic Frameworks , Prostatic Neoplasms , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Doxorubicin/pharmacology , Doxorubicin/chemistry , Animals , Humans , Cell Line, Tumor , Copper/chemistry , Copper/pharmacology , Graphite/chemistry , Graphite/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Mice , Drug Liberation , Reactive Oxygen Species/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Mice, Nude , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Xenograft Model Antitumor Assays
2.
Int J Biol Macromol ; 266(Pt 2): 131277, 2024 May.
Article En | MEDLINE | ID: mdl-38565366

Bacteria-infected wound healing has attracted widespread attention in biomedical engineering. Wound dressing is a potential strategy for repairing infectious wounds. However, the development of wound dressing with appropriate physiochemical, antibacterial, and hemostatic properties, remains challenging. Hence, there is a motivation to develop new synthetic dressings to improve bacteria-infected wound healing. Here, we fabricate a biocompatible sponge through the covalent crosslinking of collagen (Col), quaternized chitosan (QCS), and graphene oxide (GO). The resulting Col-QCS-GO sponge shows an elastic modulus of 1.93-fold higher than Col sponge due to enhanced crosslinking degree by GO incorporation. Moreover, the fabricated Col-QCS-GO sponge shows favorable porosity (84.30 ± 3.12 %), water absorption / retention (2658.0 ± 113.4 % / 1114.0 ± 65.7 %), and hemostasis capacities (blood loss <50.0 mg). Furthermore, the antibacterial property of the Col-QCS-GO sponge under near-infrared (NIR) irradiation is significantly enhanced (the inhibition rates are 99.9 % for S. aureus and 99.9 % for E. coli) due to the inherent antibacterial properties of QCS and the photothermal antibacterial capabilities of GO. Finally, the Col-QCS-GO+NIR sponge exhibits the lowest percentage of wound area (9.05 ± 1.42 %) at day 14 compared to the control group (31.61 ± 1.76 %). This study provides new insights for developing innovative sponges for bacteria-infected wound healing.


Anti-Bacterial Agents , Chitosan , Graphite , Hemostatics , Wound Healing , Animals , Rats , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bandages , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Collagen/chemistry , Collagen/pharmacology , Escherichia coli/drug effects , Graphite/chemistry , Graphite/pharmacology , Hemostasis/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Porosity , Staphylococcus aureus/drug effects , Wound Healing/drug effects
3.
Colloids Surf B Biointerfaces ; 238: 113904, 2024 Jun.
Article En | MEDLINE | ID: mdl-38603845

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.


Apoptosis , Cholestasis , Graphite , Hepatocytes , Nanocomposites , Ursodeoxycholic Acid , Graphite/chemistry , Graphite/pharmacology , Ursodeoxycholic Acid/pharmacology , Ursodeoxycholic Acid/chemistry , Animals , Apoptosis/drug effects , Nanocomposites/chemistry , Mice , Cholestasis/drug therapy , Cholestasis/pathology , Hepatocytes/drug effects , Hepatocytes/metabolism , Male , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effects , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Humans
4.
ACS Nano ; 18(16): 10829-10839, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38607639

The use of nanomaterials to improve plant immunity for sustainable agriculture is gaining increasing attention; yet, the mechanisms involved remain unclear. In contrast to metal-based counterparts, carbon-based nanomaterials do not release components. Determining how these carbon-based nanomaterials strengthen the resistance of plants to diseases is essential as well as whether shape influences this process. Our study compared single-walled carbon nanotubes (SWNTs) and graphene oxide (GO) infiltration against the phytopathogen Pseudomonas syringae pv tomato DC3000. Compared with plants treated with GO, plants primed with SWNTs showed a 29% improvement in the pathogen resistance. Upon nanopriming, the plant displayed wound signaling with transcriptional regulation similar to that observed under brushing-induced mechanostimulation. Compared with GO, SWNTs penetrated more greatly into the leaf and improved transport, resulting in a heightened wound response; this effect resulted from the tubular structure of SWNTs, which differed from the planar form of GO. The shape effect was further demonstrated by wrapping SWNTs with bovine serum albumin, which masked the sharp edges of SWNTs and resulted in a significant decrease in the overall plant wound response. Finally, we clarified how the local wound response led to systemic immunity through increased calcium ion signaling in distant plant areas, which increased the antimicrobial efficacy. In summary, our systematic investigation established connections among carbon nanomaterial priming, mechanostimulation, and wound response, revealing recognition patterns in plant immunity. These findings promise to advance nanotechnology in sustainable agriculture by strengthening plant defenses, enhancing resilience, and reducing reliance on traditional chemicals.


Graphite , Nanotubes, Carbon , Pseudomonas syringae , Pseudomonas syringae/drug effects , Nanotubes, Carbon/chemistry , Graphite/chemistry , Graphite/pharmacology , Plant Immunity/drug effects , Plant Diseases/microbiology , Plant Diseases/prevention & control , Plant Leaves/metabolism
5.
ACS Appl Mater Interfaces ; 16(15): 18300-18310, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38574271

To tackle the proliferation of pathogenic microorganisms without relying on antibiotics, innovative materials boasting antimicrobial properties have been engineered. This study focuses on the development of graphene oxide/silver (GO/Ag) nanocomposites, derived from partially reduced graphene oxide adorned with silver nanoparticles. Various nanocomposites with different amounts of silver (GO/Ag-1, GO/Ag-2, GO/Ag-3, and GO/Ag-4) were synthesized, and their antibacterial efficacy was systematically studied. The silver nanoparticles were uniformly deposited on the partially reduced graphene oxide surface, exhibiting spherical morphologies with an average size of 25 nm. The nanocomposites displayed potent antibacterial properties against both gram-positive bacteria (S. aureus and B. subtilis) and gram-negative bacteria (E. coli and S. enterica) as confirmed by minimum inhibition concentration (MIC) studies and time-dependent experiments. The optimal MIC for Gram-positive bacteria was 62.5 µg/mL and for Gram-negative bacteria was 125 µg/mL for the GO/Ag nanocomposites. Bacterial cells that encountered the nanocomposite films exhibited significantly greater inhibitory effects compared to those exposed to conventional antibacterial materials. Furthermore, the cytotoxicity of these nanocomposites was assessed using human epithelial cells (HEC), revealing that GO/Ag-1 and GO/Ag-2 exhibited lower toxicity levels toward HEC and remained compatible even at higher dilution rates. This study underscores the potential of GO/Ag-based nanocomposites as versatile materials for antibacterial applications, particularly as biocompatible wound dressings, offering promising prospects for wound healing and infection control.


Graphite , Metal Nanoparticles , Nanocomposites , Humans , Silver/pharmacology , Staphylococcus aureus , Escherichia coli , Oxides/pharmacology , Anti-Bacterial Agents/pharmacology , Graphite/pharmacology
6.
Mol Biol Rep ; 51(1): 591, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38683228

BACKGROUND: Graphene oxide nanosheets (GONS) are recognized for their role in enhancing drug delivery and effectiveness in cancer treatment. With colon cancer being a prevalent global issue and the significant side effects associated with chemotherapy, the primary treatment for colon cancer alongside surgery, there is a critical need for novel therapeutic strategies to support patients in combating this disease. Hesperetin (HSP), a natural compound found in specific fruits, exhibits anti-cancer properties. The aim of this study is to investigate the effect of GONS on the LS174t colon cancer cell line. METHODS: In this study, an anti-cancer nano-drug was synthesized by creating a hesperetin-graphene oxide nanocomposite (Hsp-GO), which was subsequently evaluated for its efficacy through in vitro cell toxicity assays. Three systems were investigated: HSP, GONS, and HSP-loaded GONS, to determine their cytotoxic and pro-apoptotic impacts on the LS174t colon cancer cell line, along with assessing the expression of BAX and BCL2. The morphology and properties of both GO and Hsp-GO were examined using scanning electron microscopy (SEM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). RESULTS: The Hsp-GO nanocomposite displayed potent cytotoxic and pro-apoptotic effects on LS174t colon cancer cells, outperforming individual treatments with HSP or GONS. Cell viability assays showed a significant decrease in cell viability with Hsp-GO treatment. Analysis of BAX and BCL2 expression revealed elevated BAX and reduced BCL2 levels in Hsp-GO treated cells, indicating enhanced apoptotic activity. Morphological analysis confirmed successful Hsp-GO synthesis, while structural integrity was supported by X-ray diffraction and FTIR analyses. CONCLUSIONS: These study highlight the potential of Hsp-GO as a promising anti-cancer nano-drug for colon cancer therapy.


Colonic Neoplasms , Drug Delivery Systems , Graphite , Hesperidin , Graphite/chemistry , Graphite/pharmacology , Humans , Hesperidin/pharmacology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Cell Line, Tumor , Drug Delivery Systems/methods , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Nanocomposites/chemistry , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/genetics
7.
Int J Biol Macromol ; 267(Pt 2): 131549, 2024 May.
Article En | MEDLINE | ID: mdl-38626838

After skin tissue trauma, wound infections caused by bacteria posed a great threat to skin repair. However, resistance to antibiotics, the current treatment of choice for bacterial infections, greatly affected the efficiency of anti-infection and wound healing. Therefore, there has been a critical need for the development of novel antimicrobial materials and advanced therapeutic methods to aid in skin repair. In this paper, rGO-PDA@ZIF-8 nanofillers were prepared by coating graphene oxide (GO) with dopamine (DA), followed by in situ growth of zeolite imidazolate framework-8 (ZIF-8). Using polyvinyl alcohol (PVA) and chitosan quaternary ammonium salt (CS) as matrix materials, along with polyethylene glycol (PEG) as a pore-forming agent, and rGO-PDA@ZIF-8 as an antimicrobial nano-filler, we successfully prepared rGO-PDA@ZIF-8/PVA/CS composite hydrogels with a directional macroporous structure using bidirectional freezing method and phase separation technique. This hydrogel exhibited excellent mechanical properties, good solubility and water retention capabilities. In addition, the hydrogel demonstrated excellent biocompatibility. Most notably, it not only exhibited excellent bactericidal effect against E. coli and S. aureus (99.1 % and 99.0 %, respectively) under the synergistic effect of intrinsic antibacterial activity and photothermal antibacterial, but also exhibited the ability to promote wound healing, making it a promising candidate for wound healing applications.


Anti-Bacterial Agents , Chitosan , Escherichia coli , Hydrogels , Polyvinyl Alcohol , Quaternary Ammonium Compounds , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Polyvinyl Alcohol/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Wound Healing/drug effects , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Porosity , Graphite/chemistry , Graphite/pharmacology , Animals , Zeolites/chemistry , Zeolites/pharmacology , Mice , Microbial Sensitivity Tests
8.
Nanotechnology ; 35(30)2024 May 07.
Article En | MEDLINE | ID: mdl-38640906

Graphene oxide nanosheet (GO) is a multifunctional platform for binding with nanoparticles and stacking with two dimensional substrates. In this study, GO nanosheets were sonochemically decorated with zinc oxide nanoparticles (ZnO) and self-assembled into a hydrogel of GO-ZnO nanocomposite. The GO-ZnO hydrogel structure is a bioinspired approach for preserving graphene-based nanosheets from van der Waals stacking. X-ray diffraction analysis (XRD) showed that the sonochemical synthesis led to the formation of ZnO crystals on GO platforms. High water content (97.2%) of GO-ZnO hydrogel provided good property of ultrasonic dispersibility in water. Ultraviolet-visible spectroscopic analysis (UV-vis) revealed that optical band gap energy of ZnO nanoparticles (∼3.2 eV) GO-ZnO nanosheets (∼2.83 eV). Agar well diffusion tests presented effective antibacterial activities of GO-ZnO hydrogel against gram-negative bacteria (E. coli) and gram-positive bacteria (S. aureus). Especially, GO-ZnO hydrogel was directly used for brush painting on biodegradable polylactide (PLA) thin films. Graphene-based nanosheets with large surface area are key to van der Waals stacking and adhesion of GO-ZnO coating to the PLA substrate. The GO-ZnO/PLA films were characterized using photography, light transmittance spectroscopy, coating stability, scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopic mapping (EDS), antibacterial test and mechanical tensile measurement. Specifically, GO-ZnO coating on PLA substrate exhibited stability in aqueous food simulants for packaging application. GO-ZnO coating inhibited the infectious growth ofE. colibiofilm. GO-ZnO/PLA films had strong tensile strength and elastic modulus. As a result, the investigation of antibacterial GO-ZnO hydrogel and GO-ZnO coating on PLA film is fundamental for sustainable development of packaging and biomedical applications.


Anti-Bacterial Agents , Escherichia coli , Graphite , Hydrogels , Polyesters , Staphylococcus aureus , Zinc Oxide , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Graphite/chemistry , Graphite/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Polyesters/chemistry , Polyesters/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Microbial Sensitivity Tests , Nanocomposites/chemistry , Ultrasonic Waves
9.
Biomater Adv ; 160: 213863, 2024 Jun.
Article En | MEDLINE | ID: mdl-38642516

To obtain the collaborative antifungal potential of nanocomposites conjugated with graphene oxide (GO), a combination of GO with chitosan (CS/GO) and GO with chitosan (CS) and polyaniline (PANI/CS/GO) was carried out. The synthesized GO-nanocomposites were recognized by several techniques. Vanillin (Van.) and cinnamaldehyde (Cinn.) were loaded on the prepared nanocomposites as antioxidants through a batch adsorption process. In vitro release study of Van. and Cinn. from the nanocomposites was accomplished at pH 7 and 25°C. The antimicrobial activity of GO, CS/GO, and PANI/CS/GO was studied against tomato Fusarium oxysporum (FOL) and Pythium debaryanum (PYD) pathogens. The loaded ternary composite PANI/CS/GO exhibited the best percent of reduction against the two pathogens in vitro studies. The Greenhouse experiment revealed that seedlings' treatment by CS/GO/Van. and PANI/CS/GO/Van significantly lowered both disease index and disease incidence. The loaded CS/GO and PANI/CS/GO nanocomposites had a positive effect on lengthening shoots. Additionally, when CS/GO/Cinn., CS/GO/Van. and PANI/CS/GO/Van. were used, tomato seedlings' photosynthetic pigments dramatically increased as compared to infected control. The results show that these bio-nanocomposites can be an efficient, sustainable, nontoxic, eco-friendly, and residue-free approach for fighting fungal pathogens and improving plant growth.


Acrolein/analogs & derivatives , Antifungal Agents , Benzaldehydes , Chitosan , Fusarium , Graphite , Nanocomposites , Solanum lycopersicum , Graphite/pharmacology , Graphite/chemistry , Solanum lycopersicum/microbiology , Nanocomposites/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Fusarium/drug effects , Chitosan/pharmacology , Chitosan/chemistry , Benzaldehydes/pharmacology , Benzaldehydes/chemistry , Plant Diseases/microbiology , Plant Diseases/prevention & control , Pythium/drug effects , Aniline Compounds/pharmacology , Aniline Compounds/chemistry , Acrolein/pharmacology , Acrolein/chemistry
10.
Int J Biol Macromol ; 266(Pt 2): 131395, 2024 May.
Article En | MEDLINE | ID: mdl-38582460

Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections. In this study, a self-healing antibacterial hydrogel (polyvinyl alcohol (PVA)-polylysine-gum arabic, PLG hydrogels) with near-infrared photothermal response was prepared by linking PVA and a novel polysaccharide-amino acid compound (PG) through borate bonding combined with freeze-thaw cycling. Subsequently, the hydrogel was modified by incorporating inorganic nanoparticles (modified graphene oxide (GM)). The experimental results showed that the PLGM3 hydrogels (PLG@GM hydrogels, 3.0 wt%) could effectively kill bacteria and promote diabetic wound tissue healing under 808-nm near-infrared laser irradiation. Therefore, this hydrogel system provides a new idea for developing novel dressings for treating diabetic wounds.


Gum Arabic , Hydrogels , Polylysine , Polyvinyl Alcohol , Wound Healing , Wound Healing/drug effects , Polyvinyl Alcohol/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Polylysine/chemistry , Polylysine/pharmacology , Gum Arabic/chemistry , Gum Arabic/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Diabetes Mellitus, Experimental , Rats , Sterilization/methods , Male , Mice , Graphite/chemistry , Graphite/pharmacology
11.
ACS Appl Bio Mater ; 7(4): 2389-2401, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38502100

Graphene-based nanomaterials, renowned for their outstanding electrical conductivity, have been extensively studied as electroconductive biomaterials (ECBs) for electrically stimulated tissue regeneration. However, using eco-friendly reducing agents like l-ascorbic acid (l-Aa) can result in lower conductive properties in these ECBs, limiting their full potential for smooth charge transfer in living tissues. Moreover, creating a flexible biomaterial scaffold using these materials that accurately mimics a specific tissue microarchitecture, such as nerves, poses additional challenges. To address these issues, this study developed a microfibrous scaffold of Bombyx mori (Bm) silk fibroin uniformly coated with graphene nanoplatelets (GNPs) through a vacuum coating method. The scaffold's electrical conductivity was optimized by varying the reduction period using l-Aa. The research systematically investigated how different reduction periods impact scaffold properties, focusing on electrical conductivity and its significance on electrically stimulated axonal growth in PC12 cells. Results showed that a 48 h reduction significantly increased surface electrical conductivity by 100-1000 times compared to a shorter or no reduction process. l-Aa contributed to stabilizing the reduced GNPs, demonstrated by a slow degradation profile and sustained conductivity even after 60 days in a proteolytic environment. ß (III) tubulin immunostaining of PC12 cells on varied silk:GNP scaffolds under pulsed electrical stimulation (ES, 50 Hz frequency, 1 ms pulse width, and amplitudes of 100 and 300 mV/cm) demonstrates accelerated axonal growth on scaffolds exhibiting higher conductivity. This is supported by upregulated intracellular Ca2+ dynamics immediately after ES on the scaffolds with higher conductivity, subjected to a prolonged reduction period. The study showcases a sustainable reduction approach using l-Aa in combination with natural Bm silk fibroin to create a highly conductive, mechanically robust, and stable silk:GNP-based aligned fibrous scaffold. These scaffolds hold promise for functional regeneration in electrically excitable tissues such as nerves, cardiac tissue, and muscles.


Bombyx , Fibroins , Graphite , Rats , Animals , Silk , Tissue Scaffolds , Graphite/pharmacology , Fibroins/pharmacology , Biocompatible Materials/pharmacology , Electric Conductivity
12.
Nanoscale ; 16(15): 7515-7531, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38498071

Despite the pharmacological arsenal approved for Multiple Sclerosis (MS), there are treatment-reluctant patients for whom cell therapy appears as the only therapeutic alternative. Myeloid-derived suppressor cells (MDSCs) are immature cells of the innate immunity able to control the immune response and to promote oligodendroglial differentiation in the MS animal model experimental autoimmune encephalomyelitis (EAE). However, when isolated and cultured for cell therapy purposes, MDSCs lose their beneficial immunomodulatory properties. To prevent this important drawback, culture devices need to be designed so that MDSCs maintain a state of immaturity and immunosuppressive function similar to that exerted in the donor organism. With this aim, we select graphene oxide (GO) as a promising candidate as it has been described as a biocompatible nanomaterial with the capacity to biologically modulate different cell types, yet its immunoactive potential has been poorly explored to date. In this work, we have fabricated GO films with two distintive redox and roughness properties and explore their impact in MDSC culture right after isolation. Our results show that MDSCs isolated from immune organs of EAE mice maintain an immature phenotype and highly immunosuppressive activity on T lymphocytes after being cultured on highly-reduced GO films (rGO200) compared to those grown on conventional glass coverslips. This immunomodulation effect is depleted when MDSCs are exposed to slightly rougher and more oxidized GO substrates (rGO90), in which cells experience a significant reduction in cell size associated with the activation of apoptosis. Taken together, the exposure of MDSCs to GO substrates with different redox state and roughness is presented as a good strategy to control MDSC activity in vitro. The versatility of GO nanomaterials in regards to the impact of their physico-chemical properties in immunomodulation opens the door to their selective therapeutic potential for pathologies where MDSCs need to be enhanced (MS) or inhibited (cancer).


Encephalomyelitis, Autoimmune, Experimental , Graphite , Multiple Sclerosis , Myeloid-Derived Suppressor Cells , Humans , Mice , Animals , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Graphite/pharmacology , Immunosuppressive Agents , Mice, Inbred C57BL
13.
Int J Nanomedicine ; 19: 2341-2357, 2024.
Article En | MEDLINE | ID: mdl-38469057

Background: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo. Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated. Results: rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES. Conclusion: The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.


Graphite , Peripheral Nerve Injuries , Rats , Mice , Animals , Rats, Sprague-Dawley , Graphite/pharmacology , Nerve Regeneration , Sciatic Nerve/injuries , Peripheral Nerve Injuries/therapy , Peripheral Nerve Injuries/pathology , Electric Stimulation/methods
14.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article En | MEDLINE | ID: mdl-38473931

This paper presents the results of research on the impact of graphene paper on selected bacterial strains. Graphene oxide, from which graphene paper is made, has mainly bacteriostatic properties. Therefore, the main goal of this research was to determine the possibility of using graphene paper as a carrier of a medicinal substance. Studies of the degree of bacterial inhibition were performed on Staphylococcus aureus and Pseudomonas aeruginosa strains. Graphene paper was analyzed not only in the state of delivery but also after the incorporation of the antibiotics ciprofloxacin, cefazolin, and methicillin into its structures. In addition, Fourier-Transform Infrared Spectroscopy, contact angle, and microscopic analysis of bacteria on the surface of the examined graphene paper samples were also performed. Studies have shown that graphene paper with built-in ciprofloxacin had a bactericidal effect on the strains of Staphylococcus aureus and Pseudomonas aeruginosa. In contrast, methicillin, as well as cefazolin, deposited on graphene paper acted mainly locally. Studies have shown that graphene paper can be used as a carrier of selected medicinal substances.


Graphite , Pseudomonas Infections , Staphylococcal Infections , Humans , Cefazolin/pharmacology , Ciprofloxacin/pharmacology , Methicillin/pharmacology , Graphite/pharmacology , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus , Bacteria , Microbial Sensitivity Tests , Pseudomonas aeruginosa
15.
PLoS One ; 19(3): e0297892, 2024.
Article En | MEDLINE | ID: mdl-38451974

Graphene has promising applications in agriculture and forestry. In the current study, six different concentrations of graphene (0mg/L, 0.01mg/L, 0.10mg/L, 1.00mg/L, 10.00mg/L, and 100.00mg/L) were used to investigate its effect on the growth and development of V. angularis plants in soil culture. The results showed that the group treated with 1.00mg/L graphene (G-1) had significantly increased plant height (19.86%), stem diameter (24.33%), and leaf area (13.69%), compared to the control group (CK). Moreover, all concentrations of graphene had positive effects on the total root length, total root surface area, and the number of root tips of V. angularis. Compared to the CK group, the G-1 group had significantly increased leaf water potential (37.89%), leaf conductivity (2.25%), and SOD, POD, and CAT activities (47.67%, 35.22%, and 199.3%, respectively). The G-1 group also showed improved leaf net photosynthetic rate, chlorophyll content, and soluble sugar content (51.28%, 24.25%, and 38.35%, respectively), compared to the CK group. Additionally, 1.00mg/L graphene led to a 23.88% increase in the podding rate and a 17.04% increase in the yield of V. angularis plants. The rhizosphere soil of V. angularis treated with 1.00mg/L graphene had a 25.14% increase in hydrolyzable nitrogen content and a 66.67% increase in available phosphorus content. RNA-seq data indicated that 1.00mg/L graphene induced the expression of photosynthesis and nitrogen transmembrane transport genes, including ATP synthase subunit b, photosystem I reaction center subunit XI, photosystem I reaction center subunit IV A, ferredoxin, and psbP-like protein 1, as well as genes for photosynthesis antenna proteins, glutamine synthetase, glutamate dehydrogenase 1, cyanate hydratase, protein fluG-like, and NRT1/PTR family, suggesting that graphene promoted the growth and development of V. angularis by enhancing the photosynthesis and nitrogen metabolism processes in V. angularis plants. Our results indicated that a suitable concentration of graphene could significantly promote the growth of V. angularis plants in soil.


Graphite , Vigna , Vigna/metabolism , Graphite/pharmacology , Graphite/metabolism , Photosynthesis/physiology , Plant Leaves/metabolism , Nitrogen/metabolism , Soil
16.
J Mater Chem B ; 12(9): 2354-2363, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38344940

Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin-hyaluronic acid (Gel-HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel-HA hydrogel surrounding the GF. The "soft" Gel-HA hydrogel and "stiff" GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel-HA/GF scaffold proliferated well and retained the CD34+CD38- immunophenotype and pluripotency, suggesting that the Gel-HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.


Bone Marrow , Graphite , Graphite/pharmacology , Hydrogels/chemistry , Hematopoietic Stem Cells , Bone Marrow Cells
17.
ACS Nano ; 18(9): 7074-7083, 2024 Mar 05.
Article En | MEDLINE | ID: mdl-38386076

Utilizing visible light for water disinfection is a more convenient, safe, and practical alternative to ultraviolet-light sterilization. Herein, we developed silver (Ag) single-atom anchored g-C3N4 (P-CN) nanosheets (Ag1/CN) and then utilized a spin-coating method to fabricate the Ag1/CN-based-membrane for effective antibacterial performance in natural water and domestic wastewater. The incorporated Ag single atom formed a Ag1-N6 motif, which increased the charge density around the N atoms, resulting in a built-in electric field ∼17.2 times stronger than that of pure P-CN and optimizing the dynamics of reactive oxygen species (ROS) production. Additionally, the Ag1-N6 motif inhibited the release of Ag ions, ensuring good biocompatibility. Based on the first-principles calculation, the adsorption energy of O2 on the Ag1/CN (-0.32 eV) was lower than that of P-CN (-0.07 eV), indicating that loaded Ag single atom can lower the energy barrier for O2 activation, generating extra *OH radicals that cooperated with *O2- to effectively neutralize bacteria. As a result, the Ag1/CN powder-catalyst with the concentration of 30 ppm demonstrated a 99.9% antibacterial efficiency against drug-resistant bacteria (Escherichia coli, Staphylococcus aureus, kanamycin-resistant Escherichia coli, and methicillin-resistant Staphylococcus aureus) under visible-light irradiation for 4 h. This efficacy was 24.8 times higher than that of the P-CN powder catalyst. Moreover, the Ag1/CN-based-membrane can maintain a 99.9% bactericidal efficiency for natural water and domestic wastewater treatment using a homemade flow device, demonstrating its potential for water disinfection. Notably, the visible-light-driven antibacterial efficiency of the Ag1/CN catalyst outperformed the majority of the reported g-C3N4-based catalysts/membranes.


Graphite , Methicillin-Resistant Staphylococcus aureus , Powders/pharmacology , Graphite/pharmacology , Anti-Bacterial Agents/pharmacology , Light , Water , Escherichia coli , Catalysis
18.
Int J Mol Sci ; 25(4)2024 Feb 17.
Article En | MEDLINE | ID: mdl-38397066

To modulate the bioactivity and boost the therapeutic outcome of implantable metallic devices, biodegradable coatings based on polylactide (PLA) and graphene oxide nanosheets (nGOs) loaded with Zinforo™ (Zin) have been proposed in this study as innovative alternatives for the local management of biofilm-associated periprosthetic infections. Using a modified Hummers protocol, high-purity and ultra-thin nGOs have been obtained, as evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigations. The matrix-assisted pulsed laser evaporation (MAPLE) technique has been successfully employed to obtain the PLA-nGO-Zin coatings. The stoichiometric and uniform transfer was revealed by infrared microscopy (IRM) and scanning electron microscopy (SEM) studies. In vitro evaluation, performed on fresh blood samples, has shown the excellent hemocompatibility of PLA-nGO-Zin-coated samples (with a hemolytic index of 1.15%), together with their anti-inflammatory ability. Moreover, the PLA-nGO-Zin coatings significantly inhibited the development of mature bacterial biofilms, inducing important anti-biofilm efficiency in the as-coated samples. The herein-reported results evidence the promising potential of PLA-nGO-Zin coatings to be used for the biocompatible and antimicrobial surface modification of metallic implants.


Anti-Infective Agents , Graphite , Nanostructures , Graphite/pharmacology , Polyesters , Coated Materials, Biocompatible/pharmacology
19.
Int J Mol Sci ; 25(3)2024 Feb 05.
Article En | MEDLINE | ID: mdl-38339205

Graphene oxide (GO) has received increasing attention in the life sciences because of its potential for various applications. Although GO is generally considered biocompatible, it can negatively impact cell physiology under some circumstances. Here, we demonstrate that the cytotoxicity of GO greatly varies depending on the cell adhesion states. Human HCT-116 cells in a non-adhered state were more susceptible to GO than those in an adherent state. Apoptosis was partially induced by GO in both adhered and non-adhered cells to a similar extent, suggesting that apoptosis induction does not account for the selective effects of GO on non-adhered cells. GO treatment rapidly decreased intracellular ATP levels in non-adhered cells but not in adhered ones, suggesting ATP depletion as the primary cause of GO-induced cell death. Concurrently, autophagy induction, a cellular response for energy homeostasis, was more evident in non-adhered cells than in adhered cells. Collectively, our observations provide novel insights into GO's action with regard to cell adhesion states. Because the elimination of non-adhered cells is important in preventing cancer metastasis, the selective detrimental effects of GO on non-adhered cells suggest its therapeutic potential for use in cancer metastasis.


Graphite , Neoplasms , Humans , Apoptosis , Graphite/pharmacology , Cell Line, Tumor , Adenosine Triphosphate/pharmacology , Oxides/pharmacology
20.
Nanomedicine ; 57: 102734, 2024 Apr.
Article En | MEDLINE | ID: mdl-38295912

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm-2), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 µg mL-1) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 µg mL-1) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 µg mL-1) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG.


Graphite , Skin Neoplasms , Humans , Graphite/pharmacology , Drug Compounding , Phototherapy , Skin Neoplasms/drug therapy , Hydrogels , Oxides , Cell Line, Tumor
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