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1.
Int J Mol Sci ; 22(15)2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34360848

ABSTRACT

Titanium is often used in the medical field and in dental implants due to its biocompatibility, but it has a high rate of leading to peri-implantitis, which progresses faster than periodontitis. Therefore, in the present study, the expression of cytokines from gingival epithelial cells by nanotitania was investigated, which is derived from titanium in the oral cavity, and the additional effect of Porphyromonasgingivalis (periodontopathic bacteria) lipopolysaccharide (PgLPS) was investigated. Ca9-22 cells were used as a gingival epithelial cell model and were cultured with nanotitania alone or with PgLPS. Cytokine expression was examined by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, cellular uptake of nanotitania was observed in scanning electron microscopy images. The expression of interleukin (IL)-6 and IL-8 significantly increased in Ca9-22 cells by nanotitania treatment alone, and the expression was further increased by the presence of PgLPS. Nanotitania was observed to phagocytose Ca9-22 cells in a dose- and time-dependent manner. Furthermore, when the expression of IL-11, related to bone resorption, was investigated, a significant increase was confirmed by stimulation with nanotitania alone. Therefore, nanotitania could be associated with the onset and exacerbation of peri-implantitis, and the presence of periodontal pathogens may worsen the condition. Further clinical reports are needed to confirm these preliminary results.


Subject(s)
Bacteroidaceae Infections/immunology , Epithelial Cells/immunology , Gingiva/immunology , Nanocomposites/adverse effects , Peri-Implantitis/immunology , Titanium/adverse effects , Cell Line , Cytokines/immunology , Epithelial Cells/cytology , Gingiva/cytology , Humans , Lipopolysaccharides/immunology , Peri-Implantitis/pathology , Porphyromonas gingivalis/immunology
2.
Biomolecules ; 10(5)2020 05 04.
Article in English | MEDLINE | ID: mdl-32375303

ABSTRACT

Recent advances in woundcare is targeted towards developing active-dressings, where multiple components are combined to provide a suitable environment for rapid healing. The aim of the present research is to study the preparation of biomimic composite wound dressings by the grafting of hydrogel on silk fibroin fabric. The swelling ability of hydrogel grafted silk fibroin fabric was optimized by changing the initiator concentration. In order to impart antimicrobial properties, these dressing are further coated sono-chemically with zinc oxide nanoparticles. The water vapor transmission rate of the prepared samples was measured. The conformation of silk fibroin proteins after grafting with hydrogel was also confirmed using Fourier Transform Infrared Spectroscopy (FTIR). The morphology of the zinc oxide-coated silk fibroin fabric and hydrogel-coated silk fibroin was studied using Scanning Electron Microscope (SEM). The antimicrobial activity of the zinc oxide-coated samples was studied against E coli. The cytocompatibility of the prepared dressing materials were evaluated using L929 fibroblast cells. MTT assay and phase contrast microscopic studies showed that the adherence, growth, and proliferation of the L929 fibroblast cells that were seeded on zinc oxide nanoparticles on the functionalized hydrogel-coated silk fibroin dressing was significantly higher than that of pure silk fibroin due to the highly porous, bio-mimic structure that allowed ease of passage of nutrients, growth factors, metabolites, and the exchange of gases which is beneficial for successful regeneration of damaged tissues. The expression of TNF-α and IL-2 were not significantly higher than that of control. The proposed composite dressing would be a promising material for wound dressing and regenerative medicine but in order to prove the efficacy of these materials, more in vivo experiments and clinical tests are required to be conducted in future.


Subject(s)
Bandages, Hydrocolloid , Fibroins/chemistry , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Zinc Oxide/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Cell Line , Cytokines/metabolism , Escherichia coli/drug effects , Fibroblasts/drug effects , Fibroblasts/metabolism , Hydrogels/chemistry , Mice , Nanocomposites/adverse effects
3.
Int J Mol Sci ; 21(7)2020 Mar 31.
Article in English | MEDLINE | ID: mdl-32244494

ABSTRACT

The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.


Subject(s)
DNA Methylation/drug effects , Nanoparticles/adverse effects , Occupational Exposure , Adult , Aged , Epigenesis, Genetic , Female , Genome, Human , Humans , Male , Middle Aged , Nanocomposites/adverse effects , Young Adult
4.
J Biomater Sci Polym Ed ; 30(16): 1489-1504, 2019 11.
Article in English | MEDLINE | ID: mdl-31322980

ABSTRACT

Cellulose is a renewable polymer quite abundant on the Earth and very attractive for applications in the construction of eco-friendly biomedical products. The aim of this study was to investigate the chemical-physical characteristics of cotton cellulose nanofiber (CCN)/chitosan nanocomposite and its cytocompatibility with human embryonic kidney cells. First, the chemical composition, swelling ratio and surface topography of the nanocomposite were evaluated. Cytocompatibility was then assessed through spreading, proliferation and viability of cells. The experimental results showed that the CCN was an effective nanomaterial agent for increasing the roughness surface of chitosan film. Cell proliferation and changes in cell morphology indicated that the nanocomposite led to improved cell spreading and growth. Cell viability did not decrease after 24 h. However, the cell survival on the nanocomposite was affected at 72 h. The results indicate that CCN/chitosan nanocomposite could be a promising biocompatible biomaterial for biomedical applications.


Subject(s)
Biocompatible Materials/adverse effects , Biocompatible Materials/chemistry , Chitosan/chemistry , Nanocomposites/adverse effects , Nanocomposites/chemistry , Nanofibers/adverse effects , Nanofibers/chemistry , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Nanostructures/chemistry , Polymers/chemistry , Surface Properties
5.
ACS Appl Mater Interfaces ; 11(25): 22129-22140, 2019 Jun 26.
Article in English | MEDLINE | ID: mdl-31144494

ABSTRACT

Photothermal therapy (PTT) based on two-dimensional (2D) nanomaterials has shown significant potential in cancer treatment. However, developing 2D nanomaterial-based theranostic agents with good biocompatibility and high therapeutic efficiency remains a key challenge. Bulk titanium (Ti) has been widely used as biomedical materials for their reputable biocompatibility, whereas nanosized Ti with a biological function remains unexplored. In this work, the 2D Ti nanosheets (NSs) are successfully exfoliated from nonlayer bulk Ti and utilized as an efficient theranostic nanoplatform for dual-modal computed tomography/photoacoustic (CT/PA) imaging-navigated PTT. Besides the excellent biocompatibility obtained by TiNSs as expected, they are found to show strong absorption ability with an extinction coefficient of 20.8 L g-1 cm-1 and high photothermal conversion ability with an efficiency of 61.5% owing to localized surface plasmon resonances, which exceeds most of other well-known photothermal agents, making it quite promising for PTT against cancer. Furthermore, the metallic property and light-heat-acoustic transformation endow 2D Ti with the strong CT/PA imaging signal and efficient cancer therapy, simultaneously. This work highlights the enormous potential of nanosized Ti in both the diagnosis and treatment of cancer. As a paradigm, this study also paves a new avenue for the elemental transition-metal-based cancer theranostics.


Subject(s)
Multimodal Imaging/methods , Nanocomposites/chemistry , Theranostic Nanomedicine/methods , Titanium/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Combined Modality Therapy , Humans , Nanocomposites/adverse effects , Nanostructures/adverse effects , Nanostructures/chemistry , Photoacoustic Techniques/methods , Surface Plasmon Resonance
6.
Med Microbiol Immunol ; 208(5): 609-629, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30291475

ABSTRACT

The aim of the present study is focused on the synthesis of Au@ZnO core-shell nanocomposites, where zinc oxide is overlaid on biogenic gold nanoparticles obtained from Hibiscus Sabdariffa plant extract. Optical property of nanocomposites is investigated using UV-visible spectroscopy and crystal structure has been determined using X-ray crystallography (XRD) technique. The presence of functional groups on the surface of Au@ZnO core-shell nanocomposites has been observed by Fourier transforms infrared (FTIR) spectroscopy. Electron microscopy studies revealed the morphology of the above core-shell nanocomposites. The synthesized nanocomposite material has shown antimicrobial and anti-biofilm activity against Staphylococcus aureus and Methicillin Resistant Staphylococcus haemolyticus (MRSH). The microbes are notorious cross contaminant and are known to cause infection in open wounds. The possible antimicrobial mechanism of as synthesized nanomaterials has been investigated against Staphylococcus aureus and obtained data suggests that the antimicrobial activity could be due to release of reactive oxygen species (ROS). Present study has revealed that surface varnishing of biosynthesized gold nanoparticles through zinc oxide has improved its antibacterial proficiency against Staphylococcus aureus, whereas reducing its toxic effect towards mouse fibroblast cells under normal and hyperglycaemic condition. Further studies have been performed in mice model to understand the wound healing efficiency of Au@ZnO nanocomposites. The results obtained suggest the possible and effective use of as synthesized core shell nanocomposites in wound healing.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Fibroblasts/drug effects , Nanocomposites/administration & dosage , Staphylococcus aureus/drug effects , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/isolation & purification , Disease Models, Animal , Gold/administration & dosage , Gold/adverse effects , Gold/isolation & purification , Hibiscus/chemistry , Mice , Nanocomposites/adverse effects , Plant Extracts/chemistry , Staphylococcal Infections/prevention & control , Staphylococcus haemolyticus/drug effects , Zinc Oxide/administration & dosage , Zinc Oxide/adverse effects , Zinc Oxide/isolation & purification
7.
Mater Sci Eng C Mater Biol Appl ; 93: 242-253, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30274056

ABSTRACT

Graphene nanocomposites have received attention for the therapy and detection of diseases. In this study, we developed a simple and green chemistry approach for synthesizing Cu2O/graphene nanocomposites (Cu2O/G) using date palm fruit syrup as a reducing agent. The graphene oxide surface anchored with Cu(OH)2 and reduced it to fabricate Cu2O-anchored graphene nanosheets using date palm fruit syrup. Physicochemical characteristics of the synthesized nanocomposites were analyzed. Scanning electron microscopy images revealed 50-70 nm Cu2O nanostructures anchored on the surface of crumpled graphene sheets. The Cu2O/G nanocomposites inhibited the gram-negative and gram-positive bacterial growth at 300 µg. When compared with Cu2O nanoparticles and graphene oxide nanosheets (GO), Cu2O/G nanocomposite exhibited outstanding bactericidal activity. The cytotoxic properties of the prepared nanocomposites were studied in human mesenchymal stem cells (hMSCs). The Cu2O/G nanocomposites did not reduced cell viability by up to 200 µg/mL and slightly induced cell death at high concentrations. However, Cu2O nanoparticles and GO have significantly reduced the cell viability in hMSCs. The microscopic images of cellular and nuclear morphology suggested that the Cu2O/G composites did not cause major changes to hMSCs. The Cu2O nanoparticles and GO remarkably triggers the cellular damages, nuclear condensation and DNA fragmentation in hMSCs. Our study results revealed that Cu2O/G has excellent antibacterial activity with good biocompatibility. Thus, Cu2O/G could be used as a promising antibacterial agent in various purposes.


Subject(s)
Anti-Bacterial Agents , Copper , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/growth & development , Graphite , Materials Testing , Mesenchymal Stem Cells/metabolism , Nanocomposites , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Copper/adverse effects , Copper/chemistry , Copper/pharmacology , Drug Evaluation, Preclinical , Graphite/adverse effects , Graphite/chemistry , Graphite/pharmacology , Humans , Mesenchymal Stem Cells/cytology , Nanocomposites/adverse effects , Nanocomposites/chemistry
8.
J Trace Elem Med Biol ; 50: 229-239, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30262284

ABSTRACT

Multidrug resistance in bacterial strains has become the greatest challenge for healthcare professionals for treating non-healing ulcers such as diabetic foot infections (DFI). Plant-mediated synthesis of S. nux-vomica-ZnO nanocomposite appears as a potential new alternative therapeutic agent that might be capable of tackling antibiotic-resistant bacterial pathogens and for treating a non-healing ulcer. The aim of the study was to investigate the antibacterial potential of S. nux-vomica-ZnO nanocomposite biosynthesised from Strychnos nux-vomica against multidrug-resistant organisms (MDROs) from DFU, wound-healing properties, and cytotoxic effects. The antibacterial potential was assessed by minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC) assays, time-kill kinetics, protein-leakage, and flow cytometric analysis. The wound-healing properties were assessed by scratch assay on mouse L929 fibroblastic cell line to quantify cell migration towards the injured area. Cytotoxicity was assessed using 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl- 2H-tetrazolium bromide (MTT) cellular viability assay on the L929 cell line and human embryonic kidney epithelial (HEK-293) cell line. Strychnos nux-vomica-ZnO nanocomposite at a size range of 10-12 nm exhibited significant bactericidal potency at a concentration of 100-200 µg/ml against MDR-Methicillin-resistant Staphylococcus aureus, MDR-Escherichia coli, MDR-Pseudomonas aeruginosa, MDR-Acinetobacter baumannii, and also against standard bacterial strains S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212. S. nux-vomica-ZnO nanocomposite also exhibited wound-healing and reduced cytotoxic properties at the antimicrobially active concentrations. Our findings thus suggested remarkable bactericidal properties of S. nux-vomica-ZnO nanocomposite and can be further exploited towards for the development of an antibacterial agent against the threatening superbugs.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanocomposites/chemistry , Animals , Anti-Bacterial Agents/adverse effects , Cell Line , Escherichia coli/drug effects , Flow Cytometry , HEK293 Cells , Humans , Mice , Microbial Sensitivity Tests , Nanocomposites/adverse effects , Staphylococcus aureus/drug effects , Wound Healing/drug effects
9.
Biomacromolecules ; 19(9): 3637-3648, 2018 09 10.
Article in English | MEDLINE | ID: mdl-30049206

ABSTRACT

In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm3 and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.


Subject(s)
Bone Regeneration , Hydrogels/chemistry , Nanocomposites/chemistry , Tissue Scaffolds/chemistry , Acrylamides/chemistry , Animals , Bone Morphogenetic Protein 2/chemistry , Cell Proliferation , Cells, Cultured , Durapatite/chemistry , Gelatin/chemistry , Hydrogels/adverse effects , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/physiology , Nanocomposites/adverse effects , Polyethylene Glycols/chemistry , Rabbits , Rats , Rats, Sprague-Dawley , Tissue Scaffolds/adverse effects
10.
Int J Mol Sci ; 19(4)2018 Apr 11.
Article in English | MEDLINE | ID: mdl-29641488

ABSTRACT

The clinical detection of carbohydrate antigen 19-9 (CA 19-9), a tumor marker in biological samples, improves and facilitates the rapid screening and diagnosis of pancreatic cancer. A simple, low cost, fast, and green synthesis method to prepare a viable carbon quantum dots/gold (CQDs/Au) nanocomposite fluorescence immunosensing solution for the detection of CA 19-9 was reported. The present method is conducted by preparing glucose-derived CQDs using a microwave-assisted method. CQDs were employed as reducing and stabilizing agents for the preparation of a CQDs/Au nanocomposite. The immobilized anti-CA 19-9-labeled horseradish peroxidase enzyme (Ab-HRP) was anchored to the surface of a CQDs/Au nanocomposite by a peptide interaction between the carboxylic and amine active groups. The CA 19-9 antigen was trapped by another monoclonal antibody that was coated on the surface of microtiter wells. The formed sandwich capping antibody-antigen-antibody enzyme complex had tunable fluorescence properties that were detected under excitation and emission wavelengths of 420 and 530 nm. The increase in fluorescence intensities of the immunoassay sensing solution was proportional to the CA 19-9 antigen concentration in the linear range of 0.01-350 U mL-1 and had a lower detection limit of 0.007 U mL-1. The proposed CQDs/Au nanocomposite immunoassay method provides a promising tool for detecting CA 19-9 in human serum.


Subject(s)
Biomarkers, Tumor/blood , CA-19-9 Antigen/blood , Gold/chemistry , Molecular Diagnostic Techniques/methods , Nanocomposites/chemistry , Quantum Dots/chemistry , Carbon/chemistry , Fluorescent Antibody Technique/methods , Humans , Nanocomposites/adverse effects
11.
Int J Nanomedicine ; 13: 917-937, 2018.
Article in English | MEDLINE | ID: mdl-29491707

ABSTRACT

BACKGROUND: To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. PURPOSE: The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. MATERIALS AND METHODS: CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). RESULTS: CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. CONCLUSIONS: The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.


Subject(s)
Dipeptides/administration & dosage , Drug Delivery Systems/methods , Nanocomposites/administration & dosage , Nanocomposites/chemistry , Administration, Ophthalmic , Animals , Biological Availability , Chitosan/administration & dosage , Chitosan/chemistry , Cornea/cytology , Cornea/drug effects , Dipeptides/chemistry , Endocytosis/drug effects , Fluorescence , Glutathione/administration & dosage , Glutathione/chemistry , Humans , Male , Nanocomposites/adverse effects , Oxazines/administration & dosage , Oxazines/pharmacokinetics , Permeability , Rabbits
12.
Biomater Sci ; 6(4): 877-884, 2018 Mar 26.
Article in English | MEDLINE | ID: mdl-29493665

ABSTRACT

In recent years, multifunctional nanoparticles have attracted much research interest in various biomedical applications such as biosensors, diagnosis, and drug delivery systems. In this study, we report an NIR imaging diagnosis and therapy nanoplatform which is developed by complexing upconversion nanoparticles (UCNP@OA) NaLuF4:Er3+,Yb3+ with nanographene oxide (NGO). The obtained nanocomposites UCNP@NGO showed excellent stability and low cell toxicity, which not only acted as upconversion luminescence (UCL) probes for tumor imaging, but also served as therapy agents by converting laser energy into thermal energy for photothermal therapy (PTT) with high photothermal conversion efficiency. This work highlights the potential of UCNP@NGO nanocomposites as an integrated theranostic nanoplatform for the UCL image combinatorial PTT of cancer, providing a promising candidate for clinical antitumor treatments.


Subject(s)
Graphite/chemistry , Lanthanoid Series Elements/chemistry , Mammary Neoplasms, Experimental/therapy , Nanocomposites/chemistry , Nanoparticles/chemistry , Phototherapy/methods , Spectroscopy, Near-Infrared/methods , Animals , Cell Line, Tumor , Cell Survival/drug effects , Female , Mice , Mice, Inbred BALB C , Nanocomposites/adverse effects , Nanoparticles/adverse effects
13.
Carbohydr Polym ; 185: 85-95, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29421063

ABSTRACT

Graphene oxide (GO) is a promising material for biomedical applications, particularly in drug delivery, due to its exceptional chemical and physical properties. In this work, an innovative GO-based carrier was developed by modifying GO with chitosan (CHI) to improve the biocompatibility, and followed by the conjugation of hyaluronic acid (HA), the target ligand for CD44, to realize the specific recognition of tumor cells and improve the efficiency of anti-tumor drug delivery. The resulting product GO-CHI-HA was loaded with an anti-cancer drug SNX-2112, which is the Hsp90 inhibitor. The total release amount and release rate of SNX-2112 were significantly higher in acidic condition than in physiological condition. GO-CHI-HA with a low concentration had little impact on the lysis of red blood cells (RBCs) and blood coagulation and showed low toxicity in A549 cells and NHBE cells. The GO-CHI-HA/SNX-2112 proved to be effective in inhibiting and killing A549 cells while having lower cytotoxicity against normal human bronchial epithelial cells (NHBE cells). Furthermore, in vivo toxicity of the materials towards vital organs in SD rats were also studied through histological examinations and blood property analyses, the results of which showed that although inflammatory response was developed in the short-term, GO-CHI-HA/SNX-2112 caused no severe long-term injury. Therefore, this drug delivery system showed great potential as an effective and safe drug delivery system with little adverse side effects for cancer therapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Graphite/chemistry , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Lung Neoplasms/drug therapy , Nanocomposites/chemistry , Polysaccharides/chemistry , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Drug Carriers/adverse effects , Hemolysis/drug effects , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Heterocyclic Compounds, 4 or More Rings/toxicity , Humans , Male , Nanocomposites/adverse effects , Rats , Rats, Sprague-Dawley
14.
Small ; 14(13): e1703809, 2018 03.
Article in English | MEDLINE | ID: mdl-29394469

ABSTRACT

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)-platinum(IV) (Pt(IV))-ZnFe2 O4 , denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near-infrared light can convert low energy photons to high energy ones, which act as the UV-vis source to simultaneously mediate the PDT effect and Fenton's reaction of ZnFe2 O4 nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb3+ and Fe3+ in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X-ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all-in-one imaging-guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.


Subject(s)
Glutathione/chemistry , Glutathione/metabolism , Multimodal Imaging/methods , Nanocomposites/chemistry , Nanoparticles/chemistry , Platinum/chemistry , Contrast Media/chemistry , HeLa Cells , Hemolysis/drug effects , Humans , Magnetic Resonance Imaging , Nanocomposites/adverse effects , Photochemotherapy/methods , Prodrugs/chemistry , Tomography, X-Ray Computed
15.
Biomater Sci ; 6(4): 842-853, 2018 Mar 26.
Article in English | MEDLINE | ID: mdl-29485660

ABSTRACT

The surface of a mesoporous magnesium-calcium-silicate (m-MCS)/polyetheretherketone (PK) composite (MPC) was modified by sand blasting, and genistein (GS) was loaded inside the nanopores of the m-MCS on the modified MPC (MPCm) surface. The results showed that compared with MPC, the surface roughness and hydrophilcity of MPCm obviously improved with more m-MCS exposed on its surface. Moreover, no obvious differences in surface roughness and hydrophilcity were found between MPCm and GS loaded MPCm (MPCm-Ge), and both of them possessed an improved apatite mineralization ability in simulated body fluid solution (SBF) compared with MPC, indicating excellent surface bioactivity. Moreover, the MPCm obviously stimulated the adhesion, proliferation, differentiation and gene expressions of MC3T3-E1 cells compared with MPC, and the sustained-release of GS from the MPCm-Ge surface further significantly promoted the cell proliferation, differentiation and gene expression. According to the Micro-CT, histological and SEM analysis, the results demonstrated that the MPCm obviously improved osteogenesis and enhanced osseointegration in vivo compared with MPC, and the release of GS from the MPCm-Ge surface further significantly improved osteogenesis and enhanced osseointegration. In summary, the significant promotion of cell responses in vitro, and the improvements of osteogenesis and the enhancement of osseointegration in vivo were attributed to the effects of surface bioactivity and GS sustained-release from the MPCm-Ge surface. Therefore, MPCm-Ge would be a potential candidate for orthopedic and dental applications.


Subject(s)
Genistein/administration & dosage , Ketones/chemistry , Nanocomposites/chemistry , Osseointegration/drug effects , Osteogenesis/drug effects , Polyethylene Glycols/chemistry , 3T3 Cells , Animals , Benzophenones , Calcium/chemistry , Cell Proliferation/drug effects , Dogs , Drug Liberation , Genistein/pharmacokinetics , Genistein/pharmacology , Genistein/therapeutic use , Magnesium/chemistry , Male , Mice , Nanocomposites/adverse effects , Polymers , Silicates/chemistry
16.
Biomater Sci ; 6(2): 398-406, 2018 Jan 30.
Article in English | MEDLINE | ID: mdl-29337327

ABSTRACT

Cutaneous chronic wounds remain a major clinical challenge which requires the development of novel wound dressings. Previously, we showed that collagen-silica nanocomposites consisting of polyethyleneimine (PEI)-DNA complexes associated with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained production and release of biomolecules. Herein, we further explored the possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti-inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect was evaluated in an in vitro inflammation model carried out by LPS (lipopolysaccharide) activation of macrophages embedded in collagen gel. The IL-10 synthesis from nanocomposites was detected over one week in the range of 200-400 pg mL-1 and reached a maximum at day 5 without any observed cytotoxic effects. PEI10-SiNP outperformed free PEI10 and PEI25-SiNP, implying that the introduction of SiNP improved the transfection efficiency of low Mw of PEI. In addition, the structure and mechanical properties of collagen-silica nanocomposites were stable over one week. Subsequently, the ability of nanocomposites to modulate inflammation was tested in a 3D model of inflammation. The decrease of TNF-α and IL-1ß gene expression by 20-80% indicated successful inhibition of inflammation by IL-10 released from nanocomposites. Taken together, the nanocomposites are capable of producing effective doses of IL-10 which inhibit the synthesis of pro-inflammatory cytokines and favor the expression of wound healing cytokines. Therefore, the as-constructed 3D gene delivery system represents a promising strategy for the controlled release of therapeutic biomolecules favoring cutaneous wound healing.


Subject(s)
Gene Transfer Techniques , Interleukin-10/genetics , Nanocomposites/chemistry , Skin/injuries , Wound Healing , Animals , Cell Line , Collagen/chemistry , Genetic Therapy/methods , Humans , Interleukin-10/metabolism , Mice , Nanocomposites/adverse effects , Silicon Dioxide/chemistry
17.
Carbohydr Polym ; 183: 165-172, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29352871

ABSTRACT

We report a novel approach for fabricating nanocomposite polysaccharide-based carriers for sustained delivery of poorly-water-soluble drugs by embedding stabilized core-shell micelles (SPM) possessing hydrophobic cores into super-macroporous hydroxypropyl cellulose (HPC) cryogels. Firstly, nano-sized SPM were synthesized by loading and photochemical crosslinking of pentaerythritoltetraacrylate (PETA) in poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO19PPO29PEO19) core-shell micelles. Next, HPC cryogels containing different amount of SPM were fabricated by combination of cryogenic treatment and photo-crosslinking. A crosslinking agent, N,N'-methylenebisacrylamide, was used to enhance the density of polymer network. The effect of SPM concentration on gel fraction yield, swelling degree, cryogel morphology and mechanical properties were studied. Nanocomposite cryogels were loaded with curcumin and their encapsulation efficiency and drug release profile as a function of SPM content were investigated. The cytotoxic effect of blank and curcumin loaded nanocomposite cryogels was assessed as well.


Subject(s)
Cellulose/analogs & derivatives , Cryogels/chemistry , Micelles , Nanocomposites/chemistry , Acrylamides/chemistry , Cell Line, Tumor , Curcumin/administration & dosage , Drug Carriers/chemistry , HEK293 Cells , Humans , Methacrylates/chemistry , Nanocomposites/adverse effects , Polyethylene Glycols/chemistry , Propylene Glycols/chemistry
18.
J Biomed Mater Res B Appl Biomater ; 106(5): 2029-2036, 2018 07.
Article in English | MEDLINE | ID: mdl-29076251

ABSTRACT

While Ag nanoparticles hold great promise for broad spectrum antibacterial activity, the potential risks of Ag nanoparticles (NPs) on human health remain a challenge. In this study, Ag/Fe3 O4 composites have been successfully prepared and characterized by transmission electron microscopy, X-ray powder diffraction, and Fourier-transform infrared spectroscopy, and their magnetic and antibacterial properties have been assessed. In vivo results show that the antibacterial effect of 500 µg/mL Ag/Fe3 O4 nanocomposites was significantly higher than that of 1000 µg/mL AgNPs after 72 h of treatment (p < 0.01). Hematoxylin and eosin (HE) staining showed that squamous epithelium and dermis collagen fibers formed in the Ag/Fe3 O4 group after 8 days treatment. Wound closure was significantly better for the Ag/Fe3 O4 group than for the AgNPs group. On the other hand, there was less Ag in blood, liver, and kidney in the Ag/Fe3 O4 group, as more Ag was retained in the wound. According to lactate dehydrogenase, γ-glutamyl transpeptidase, and reactive oxygen species results, Ag/Fe3 O4 nanocomposites caused less unwanted side-effects. This work presents a new paradigm to reduce the unwanted side-effects of AgNPs and improve their antibacterial activity, providing a new avenue for wound healing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2029-2036, 2018.


Subject(s)
Anti-Bacterial Agents , Ferrosoferric Oxide , Nanocomposites/chemistry , Reactive Oxygen Species/metabolism , Silver , Wound Infection/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Ferrosoferric Oxide/chemistry , Ferrosoferric Oxide/pharmacology , Male , Microscopy, Electron, Transmission , Molybdoferredoxin , Nanocomposites/adverse effects , Nanocomposites/ultrastructure , Rats , Rats, Sprague-Dawley , Silver/chemistry , Silver/pharmacology , Wound Healing/drug effects , Wound Infection/pathology , X-Ray Diffraction
19.
Int J Biol Macromol ; 109: 273-286, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29248555

ABSTRACT

Chitosan the second most abundant next to cellulose, naturally occurring amino polysaccharide, derived as a deacetylated form of chitin. Its nontoxic, biocompatible, antibacterial and biodegradable properties have led to significant research towards biomedical and pharmaceutical applications, such as drug delivery, tissue engineering, wound-healing dressing etc. The primary amine group in chitosan are responsible for its various properties such as cationic nature, controlled drug release, muco-adhesion, in situ gelation, antimicrobial, permeation enhancement etc. This review discusses the various forms of chitosan materials such as beads, films, microspheres, nanoparticles, nanofibers, hydrogels, nanocomposites, etc. as drug delivery device and attempted to report the vast literature available on chitosan based materials in drug delivery applications. Moreover, chitosan derivatives and chitosan nanocomposites with different nanofillers and its application in drug delivery have also been reviewed.


Subject(s)
Chitosan/chemistry , Drug Carriers , Drug Delivery Systems , Nanocomposites/chemistry , Animals , Biocompatible Materials/adverse effects , Biocompatible Materials/chemistry , Biopolymers/chemistry , Drug Carriers/adverse effects , Drug Carriers/chemistry , Humans , Materials Testing , Nanocomposites/adverse effects
20.
Biomacromolecules ; 18(10): 3222-3232, 2017 Oct 09.
Article in English | MEDLINE | ID: mdl-28892612

ABSTRACT

Medium chain-length polyhydroxyalkanoates (mPHAs) are flexible elastomeric biopolymers with valuable properties for biomedical applications like artificial arteries and other medical implants. However, an environmentally friendly and high productivity process together with the tuning of the mechanical and biological properties of mPHAs are mandatory for this purpose. Here, for the first time, a melt processing technique was applied for the preparation of bionanocomposites starting from poly(3-hydroxyoctanoate) (PHO) and bacterial cellulose nanofibers (BC). The incorporation of only 3 wt % BC in PHO improved its thermal stability with 25 °C and reinforced it, increasing the Young's modulus with 76% and the tensile strength with 44%. The percolation threshold calculated with the aspect ratio of the fibers after melt processing was very low and close to 3 wt %. We showed that this bionanocomposite is able to preserve the ductile behavior during storage, no important aging being noted between 3 h and one month after compression-molding. Moreover, this study is the first to investigate the melt processability of PHO nanocomposite for tube extrusion. In addition, biocompatibility study showed no proinflammatory immune response and better cell adhesion for PHO/BC nanocomposite with 3 wt % BC and demonstrated the high feasibility of this bionanocomposite for in vivo application of tissue-engineered blood vessels.


Subject(s)
Artificial Organs , Biocompatible Materials/chemistry , Cellulose/analogs & derivatives , Polyhydroxyalkanoates/chemistry , Polysaccharides, Bacterial/chemistry , Biocompatible Materials/adverse effects , Cell Adhesion/drug effects , Cell Line , Elastic Modulus , Freezing , Humans , Nanocomposites/adverse effects , Nanocomposites/chemistry , Nanofibers/adverse effects , Nanofibers/chemistry , Pseudomonas putida/chemistry , Tensile Strength
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