Human periodontal ligament stem cell sheets activated by graphene oxide quantum dots repair periodontal bone defects by promoting mitochondrial dynamics dependent osteogenic differentiation.

BACKGROUND: Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation. RESULTS: There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission. CONCLUSIONS: Overall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation.

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent.

Regulating Frozen Electrolyte Structure with Colloidal Dispersion for Low Temperature Aqueous Batteries.

Electrolyte freezing under low temperatures is a critical challenge for the development of aqueous batteries (ABs). While lowering the freezing point of the electrolyte has caught major research efforts, limited attention has been paid to the structural evolution during the electrolyte freezing process and regulating the frozen electrolyte structure for low temperature ABs. Here, we reveal the formation process of interconnected liquid regions for ion transport in frozen electrolytes with various in situ variable-temperature technologies. More importantly, the low-temperature performance of ABs was significantly improved with the colloidal electrolyte design using graphene oxide quantum dots (GOQDs), which effectively inhibits the growth of ice crystals and expands the interconnected liquid regions for facial ion transport. This work provides new insights and a promising strategy for the electrolyte design of low-temperature ABs.

Graphene-Based Nanomaterials for Biomedical Imaging.

Graphene is sp2-hybridized carbon structure-based two-dimensional (2D) sheet. Graphene-based nanomaterials possess several features such as unique mechanical, electronic, thermal, and optical properties, high specific surface area, versatile surface functionalization, and biocompatibility, which attracted researcher's interests in various fields including biomedicine. In this chapter, we particularly focused on the biomedical imaging applications of graphene-based nanomaterials like graphene oxide (GO), reduced graphene oxide (rGO), graphene quantum dots (GQDs), graphene oxide quantum dots (GOQDs), and other derivatives, which utilize their outstanding optical properties. There are some biomedical imaging modalities using Graphene-based Nanomaterials, among which we will highlight fluorescence imaging, Raman imaging, magnetic resonance imaging, and photoacoustic imaging. We also discussed the brief perspectives and future application related to them.

Quantum dots bind nanosheet to promote nanomaterial stability and resist endotoxin-induced fibrosis and PM2.5-induced pneumonia.

Endotoxin lipopolysaccharide (LPS) is a harmful substance commonly found in various environments that causes lung fibrosis. Exposure to PM2.5 also increases the risk of respiratory diseases. Through sulfur-carbon bonds and the edge S effect, GOQDs were used to bind in single-layer molybdenum disulfide (SLMoS2) nanosheets to synthesize SLMoS2@GOQDs heterojunction structures. GOQDs doping greatly increased the water solubility and stabilized of SLMoS2. SLMoS2@GOQDs with catalase-like activity protected cells from ultrastructural and cytomembrane damage and apoptosis induced by LPS. Moreover, the doping of GOQDs enhanced the escape of SLMoS2@GOQDs from cellular uptake and suppressed the release of Mo ions. Nanosheet-cell interface interactions that were regulated by quantum dots supported these positive effects. Immunofluorescence analysis and cell imaging confirmed that the nanomaterial protected against cell injury by regulating the canonical Wnt/ß-catenin pathway and the secretion of relevant cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Moreover, SLMoS2@GOQDs also mitigated pneumonia caused by PM2.5 in vivo. Collectively, our findings not only provide a simple and effective approach to control lung diseases (caused by LPS or PM2.5), but also reveal the potential value of heterojunction materials in the fields of toxicology and human health, boosting the application of nanotechnology in the fields of ecotoxicology and environmental safety.

Advances in Biologically Applicable Graphene-Based 2D Nanomaterials.

Climate change and increasing contamination of the environment, due to anthropogenic activities, are accompanied with a growing negative impact on human life. Nowadays, humanity is threatened by the increasing incidence of difficult-to-treat cancer and various infectious diseases caused by resistant pathogens, but, on the other hand, ensuring sufficient safe food for balanced human nutrition is threatened by a growing infestation of agriculturally important plants, by various pathogens or by the deteriorating condition of agricultural land. One way to deal with all these undesirable facts is to try to develop technologies and sophisticated materials that could help overcome these negative effects/gloomy prospects. One possibility is to try to use nanotechnology and, within this broad field, to focus also on the study of two-dimensional carbon-based nanomaterials, which have excellent prospects to be used in various economic sectors. In this brief up-to-date overview, attention is paid to recent applications of graphene-based nanomaterials, i.e., graphene, graphene quantum dots, graphene oxide, graphene oxide quantum dots, and reduced graphene oxide. These materials and their various modifications and combinations with other compounds are discussed, regarding their biomedical and agro-ecological applications, i.e., as materials investigated for their antineoplastic and anti-invasive effects, for their effects against various plant pathogens, and as carriers of bioactive agents (drugs, pesticides, fertilizers) as well as materials suitable to be used in theranostics. The negative effects of graphene-based nanomaterials on living organisms, including their mode of action, are analyzed as well.

Photo-responsive degradable hollow mesoporous organosilica nanoplatforms for drug delivery.

BACKGROUND: Stimulus-responsive degradable mesoporous organosilica nanoparticles (MONs) have shown great promise as drug carriers via enhancing the efficiency of drug delivery and accelerating the degradation of nanocarriers. However, it remains a great challenge to develop novel light-enabled spatial and temporal degradable MONs with both superior responsiveness for efficient anti-cancer drug delivery and safe exocytosis. RESULTS: We report a novel photo-responsive degradable hollow mesoporous organosilica nanoplatform (HMONs@GOQD). The platform is based on organosilica nanoparticles (HMONs) containing singlet oxygen (1O2)-responsive bridged organoalkoxysilanes and wrapped graphene oxide quantum dots (GOQDs). The unique hollow mesoporous structure of the HMONs guarantees an excellent drug loading and release profile. During light irradiation, 1O2 produced by the GOQDs leads to the degradation of the organosilica nanoparticles, resulting in enhanced local drug release. CONCLUSIONS: We carried out in vitro and in vivo experiments using DOX as a model drug; DOX-HMONs@GOQDs exhibited high biocompatibility, accelerated degradation, and superior therapeutic efficacy during light irradiation, indicating a promising platform for clinical cancer therapy.

High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment.

Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca2+. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.

Preparation of graphene oxide quantum dots from waste toner, and their application to a fluorometric DNA hybridization assay.

A one-pot hydrothermal method was developed for the synthesis of graphene oxide quantum dots (GOQDs). It is making use of toner waste as the precursor and H2O2 as the oxidant. Synthesis takes 4 h and does not require strong acids or complex purification steps and does not produce environmentally harmful metal ions. The GOQDs display blue fluorescence with excitation/emission maxima at 340/445 nm. The feasibility of detecting specific DNA sequence was promoted using polyethyleneimine to modify the GOQDs surface. A method was developed to recognized a specific DNA sequence. This is based on electrostatic aggregation of GOQDs and ssDNA labeled with Dabcyl at the 3' end, which promotes fluorescence quenching of GOQDs. The possible fluorescence quenching mechanism (which is mainly dynamic) was investigated using the Stern-Volmer equation. When a target sequence was added, which is complementary to the ssDNA, the dabcyl-labeled ssDNA is released due to strict complementary base pairing. This promotes fluorescence recovery of GOQDs. The assay has a 0.17 nM detection limit and a linear range of 0.5-30 nM. The method was used to quantify specific DNA sequences from extracts of genetically modified plant tissues. Graphical abstract Graphene oxide quantum dots (GOQDs) were synthesized by one-pot hydrothermal method using waste toner, and the surface was modified by polyethyleneimine (PEI). Through the interaction of PEI-GOQDs with Dabcyl-DNA single strands to dynamically quench the fluorescence of GOQDs. Based on DNA hybridization technology, we established specific DNA sequence detection nanoprobe.

A triple signal amplification method for chemiluminescent detection of the cancer marker microRNA-21.

Mesoporous silica nanospheres (MSNs) are used in a triple signal amplification chemiluminescent (CL) assay for microRNA-21. It is based on (a) the synergistic amplification via loading and controlled-release of signal reagents by MSNs, (b) target recycling amplification, and (c) the enhancement effect of graphene oxide quantum dots (GOQD). CL is generated by the bis(2,4,6-trichlorophenyl) oxalate (TCPO) and H2O2 reaction in the presence of the fluorophore rhodamine B (RB). RB is firstly loaded into the pores of MSNs modified with amino groupsand coupled with ssDNA. Then, the pores are capped by GOQD. Upon the addition of microRNA-21 into the system, the designed ssDNA assumes a double stranded structure. With the aid of duplex-specific nuclease, the double strand structure is cleaved and the free microRNA-21 enters into the next cycling process to combine with other ssDNA forming double strand structures. After several cycling process, amounts of GOQDs departing from the surface of MSNs cause the opening of the pores of MSNs and the release of RB causes the CL of TCPO-H2O2 reaction system. Free GOQDs can lead to a further CL enhancement. By this method, even a low amount of microRNA-21 leads to a large number of released RB molecules and triggers high-intensity CL. The method was applied in an assay where the CL signal increases linearly with the logarithm of the microRNA-21 concentration in the range of 0.005-50 pmol L-1 and the detection limit is 1.7 fmol L-1 (at 3σ). Graphical abstract Schematic presentation of a triple signal amplification chemiluminescence (CL) analysis platform based on rodamine B (RB) loading and controlled release, target recycling amplification and graphene oxide quantum dots (GOQD) as the enhancer for analysis of microRNA-21 in human serum.

Graphene Oxide Quantum Dots Exfoliated From Carbon Fibers by Microwave Irradiation: Two Photoluminescence Centers and Self-Assembly Behavior.

Graphene oxide quantum dots (GOQDs) attract great attention for their unique properties and promising application potential. The difficulty in the formation of a confined structure, and the numerous and diverse oxygen-containing functional groups results in a low emission yield to GOQDs. Here, GOQDs with a size of about 5 nm, exfoliated from carbon fibers by microwave irradiation, are detected and analyzed. The exfoliated GOQDs are deeply oxidized and induce large numbers of epoxy groups and ether bonds, but only a small amount of carbonyl groups and hydroxyl groups. The subdomains of sp2 clusters, involving epoxy groups and ether bonds, are responsible for the two strong photoluminescence emissions of GOQDs under different excitation wavelengths. Moreover, GOQDs tend to self-assemble at the edges of their planes to form self-assembly films (SAFs) with the evaporation of water. SAFs can further assemble into different 3D patterns with unique microstructures such as sponge bulk, sponge ball, microsheet, sisal, and schistose coral, which are what applications such as supercapacitors, cells, catalysts, and electrochemical sensors need. This method for preparation of GOQDs is easy, quick, and environmentally friendly, and this work may open up new research interests about GOQDs.

Synergistic Targeting and Efficient Photodynamic Therapy Based on Graphene Oxide Quantum Dot-Upconversion Nanocrystal Hybrid Nanoparticles.

Locating nanotherapeutics at the active sites, especially in the subcellular scale, is of great importance for nanoparticle-based photodynamic therapy (PDT) and other nanotherapies. However, subcellular targeting agents are generally nonspecific, despite the fact that the accumulation of a nanoformulation at active organelles leads to better therapeutic efficacy. A PDT nanoformulation is herein designed by using graphene oxide quantum dots (GOQDs) with rich functional groups as both the supporter for dual targeting modification and the photosensitizer for generating reactive oxygen species, and upconversion nanoparticles (UCNs) as the transducer of excitation light. A tumor-targeting agent, folic acid, and a mitochondrion-targeting moiety, carboxybutyl triphenylphosphonium, are simultaneously attached onto the UCNs-GOQDs hybrid nanoparticles by surface modification, and a synergistic targeting effect is obtained for these nanoparticles according to both in vitro and in vivo experiments. More significant cell death and a higher extent of mitochondrion damage are observed compared to the results of UCNs-GOQDs nanoparticles with no or just one targeting moiety. Furthermore, the PDT efficacy on tumor-bearing mice is also effectively improved. Overall, the current work presents a synergistic strategy to enhance subcellular targeting and the PDT efficacy for cancer therapy, which may also shed light on other kinds of nanotherapies.

Minimization of Ion-Solvent Clusters in Gel Electrolytes Containing Graphene Oxide Quantum Dots for Lithium-Ion Batteries.

This study uses graphene oxide quantum dots (GOQDs) to enhance the Li+ -ion mobility of a gel polymer electrolyte (GPE) for lithium-ion batteries (LIBs). The GPE comprises a framework of poly(acrylonitrile-co-vinylacetate) blended with poly(methyl methacrylate) and a salt LiPF6 solvated in carbonate solvents. The GOQDs, which function as acceptors, are small (3-11 nm) and well dispersed in the polymer framework. The GOQDs suppress the formation of ion-solvent clusters and immobilize PF6- anions, affording the GPE a high ionic conductivity and a high Li+ -ion transference number (0.77). When assembled into Li|electrolyte|LiFePO4 batteries, the GPEs containing GOQDs preserve the battery capacity at high rates (up to 20 C) and exhibit 100% capacity retention after 500 charge-discharge cycles. Smaller GOQDs are more effective in GPE performance enhancement because of the higher dispersion of QDs. The minimization of both the ion-solvent clusters and degree of Li+ -ion solvation in the GPEs with GOQDs results in even plating and stripping of the Li-metal anode; therefore, Li dendrite formation is suppressed during battery operation. This study demonstrates a strategy of using small GOQDs with tunable properties to effectively modulate ion-solvent coordination in GPEs and thus improve the performance and lifespan of LIBs.

Ultrasonic assisted magnetic dispersive solid phase microextraction for pre concentration of serotonin-norepinephrine reuptake inhibitor drugs.

A simple and sensitive ultrasonic assisted magnetic dispersive solid phase microextraction method (UAMDSPME) coupled with high performance liquid chromatography was developed to determine serotonin-norepinephrine reuptake inhibitor drugs including duloxetine (DUL), venlafaxine (VEN) and atomoxetine (ATO) in human urine, river water and well water samples. A novel and efficient SPME sorbent, magnetic p-Phenylenediamine functionalized reduced graphene oxide Quantum Dots@ Ni nanocomposites (MrGOQDs-PD@ Ni), was prepared and applied for extraction of the analytes. Several effective parameters on the extraction efficiency of the analytes were investigated and optimized with experimental design approach. The performance of MrGOQDs-PD@ Ni as the SPME sorbent for the extraction of DUL, VEN and ATO was then compared with magnetic graphene oxide (MGO@Fe3O4) and magnetic reduced graphene oxide (MrGO@ Ni). Under the optimized conditions for the MrGOQDs-PD@ Ni sorbent, the intra-day relative standard deviations (RSDs, n = 5) and the limits of detections (LODs) were lower than 4.6% and 1.1 ngmL-1, respectively. Moreover, the good linear ranges were observed in wide concentration ranges with R-squared larger than 0.9878. Finally, the enrichment factors in the range of 137-183 and the recovery percentage in the range of 89.2-94.8% were obtained to determine the analytes in the real samples.

Zero valent Fe-reduced graphene oxide quantum dots as a novel magnetic dispersive solid phase microextraction sorbent for extraction of organophosphorus pesticides in real water and fruit juice samples prior to analysis by gas chromatography-mass spectrometry.

A selective and sensitive magnetic dispersive solid-phase microextraction (MDSPME) coupled with gas chromatography-mass spectrometry was developed for extraction and determination of organophosphorus pesticides (Sevin, Fenitrothion, Malathion, Parathion, and Diazinon) in fruit juice and real water samples. Zero valent Fe-reduced graphene oxide quantum dots (rGOQDs@ Fe) as a new and effective sorbent were prepared and applied for extraction of organophosphorus pesticides using MDSPME method. In order to study the performance of this new sorbent, the ability of rGOQDs@ Fe was compared with graphene oxide and magnetic graphene oxide nanocomposite by recovery experiments of the organophosphorus pesticides. Several affecting parameters in the microextraction procedure, including pH of donor phase, donor phase volume, stirring rate, extraction time, and desorption conditions such as the type and volume of solvents and desorption time were thoroughly investigated and optimized. Under the optimal conditions, the method showed a wide linear dynamic range with R-square between 0.9959 and 0.9991. The limit of detections, the intraday and interday relative standard deviations (n = 5) were less than 0.07 ngmL-1, 4.7, and 8.6%, respectively. The method was successfully applied for extraction and determination of organophosphorus pesticides in real water samples (well, river and tap water) and fruit juice samples (apple and grape juice). The obtained relative recoveries were in the range of 82.9%-113.2% with RSD percentages of less than 5.8% for all the real samples.

From Graphite to Graphene Oxide and Graphene Oxide Quantum Dots.

Many methods have been reported for synthesizing graphene oxide (GO) and graphene oxide quantum dots (GOQDs) where a tedious operational procedure and long reaction time are generally required. Herein, a facile one-pot solvothermal method that allows selective synthesis of pure GO and pure GOQDs, respectively is demonstrated. What is more, the final product of either GO or differently sized GOQDs can be easily controlled by adjusting the reaction temperatures or reactant ratios, which is also feasible when enlarged to gram scale. The 2.5 nm GOQDs show excellent photoluminescence that can be utilized for bioimaging or distinctive detection of Eu3+ and Tb3+ from their respective mixtures with other rare earth and/or transition metal ions, at sub-ppm level.

Is the Chain of Oxidation and Reduction Process Reversible in Luminescent Graphene Quantum Dots?

Graphene-based quantum dots (QDs) have received a tremendous amount of attention as a new type of light-emitting materials. However, their luminescence origins remain controversial due to extrinsic states of the impurities and disorder structures. Especially, the function of oxygen-contents should be understood and controlled as a crucial element for tuning the optical properties of graphene-based QDs. Herein, a series of graphene oxide QDs (GOQDs) with different amounts of oxygen-contents are first synthesized via a direct oxidation route of graphite nanoparticle and thoroughly compared with a series of reduced GOQDs (rGOQDs) prepared by the conventional chemical reduction. Irreversible emission and different carrier dynamics are observed between the GOQDs and rGOQDs, although both routes show a similar tendency with regard to the variation of oxygen-functional components. Their luminescence mechanisms are closely associated with different atomic structures. The mechanism for the rGOQDs can be associated with a formation of small sp(2) nanodomains as luminescent centers, whereas those of GOQDs may be composed of oxygen-islands with difference sizes depending on oxidation conditions surrounded by a large area of sp(2) bonding. Important insights for understanding the optical properties of graphene-based QDs and how they are affected by oxygen-functional groups are shown.

A self-assembled graphene oxide adjuvant induces both enhanced humoral and cellular immune responses in influenza vaccine.

Antiviral vaccine is essential for preventing and controlling virus spreading, along with declining morbidity and mortality. A major challenge in effective vaccination lies in the ability to enhance both the humoral and cellular immune responses by adjuvants. Herein, self-assembled nanoparticles based on graphene oxide quantum dots with components of carnosine, resiquimod and Zn2+ ions, namely ZnGC-R, are designed as a new adjuvant for influenza vaccine. With its high capability for antigen-loading, ZnGC-R enhances antigen utilization, improves DC recruitment, and activates antigen-presenting cells. Single cell analysis of lymphocytes after intramuscular vaccination revealed that ZnGC-R generated multifaceted immune responses. ZnGC-R stimulated robust CD4+CCR7loPD-1hi Tfh and durable CD8+CD44hiCD62L- TEM immune responses, and simultaneously promoted the proliferation of CD26+ germinal center B cells. Besides, ZnGC-R elicited 2.53-fold higher hemagglutination-inhibiting antibody than commercial-licensed aluminum salt adjuvant. ZnGC-R based vaccine induced 342% stronger IgG antibody responses compared with vaccines with inactivated virus alone, leading to 100% in vivo protection efficacy against the H1N1 influenza virus challenge.

Multistage Nanocarrier Based on an Oil Core-Graphene Oxide Shell.

Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier.

Chondroitin sulfate/silk fibroin hydrogel incorporating graphene oxide quantum dots with photothermal-effect promotes type H vessel-related wound healing.

Chronic wounds with bacterial infection present formidable clinical challenges. In this study, a versatile hydrogel dressing with antibacterial and angiogenic activity composite of silk fibroin (SF), chondroitin sulfate (CS), and graphene oxide quantum dots (GOQDs) is fabricated. GOQDs@SF/CS (GSC) hydrogel is rapidly formed through the enzyme catalytic action of horseradish peroxidase. With the incorporation of GOQDs both gelation speed and mechanical properties have been enhanced, and the photothermal characteristics of GOQDs in GSC hydrogel enabled bacterial killing through photothermal treatment (PTT) at ∼51 °C. In vitro studies show that the GSC hydrogels demonstrate excellent antibacterial performance and induce type H vessel differentiation of endothelial cells via the activated ERK1/2 signaling pathway and upregulated SLIT3 expression. In vivo results show that the hydrogel significantly promotes type H vessels formation, which is related to the collagen deposition, epithelialization and, ultimately, accelerates the regeneration of infected skin defects. Collectively, this multifunctional GSC hydrogel, with dual action of antibacterial efficacy and angiogenesis promotion, emerges as an innovative skin dressing with the potential for advancing in infected wound healing.