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1.
Chem Commun (Camb) ; 56(10): 1493-1496, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31922159

RESUMO

This study presents the synthesis of 5,6-fused bicyclic conjugated energetic compounds through a combined strategy of anchoring the catenated nitrogen-atom chain and introducing vicinal C-amino and C-nitro groups into a tetrazolo-pyridazine ring. Their crystal structures were confirmed by single crystal X-ray diffraction. Both compounds display good thermal stability, high energetic properties and low sensitivities as energetic materials.

4.
Nat Commun ; 10(1): 4490, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582736

RESUMO

The application of photothermal therapy to treat bacterial infections remains a challenge, as the high temperatures required for bacterial elimination can damage healthy tissues. Here, we develop an exogenous antibacterial agent consisting of zinc-doped Prussian blue (ZnPB) that kills methicillin-resistant Staphylococcus aureus in vitro and in a rat model of cutaneous wound infection. Local heat triggered by the photothermal effect accelerates the release and penetration of ions into the bacteria, resulting in alteration of intracellular metabolic pathways and bacterial killing without systemic toxicity. ZnPB treatment leads to the upregulation of genes involved in tissue remodeling, promotes collagen deposition and enhances wound repair. The efficient photothermal conversion of ZnPB allows the use of relatively few doses and low laser flux, making the platform a potential alternative to current antibiotic therapies against bacterial wound infections.


Assuntos
Antibacterianos/administração & dosagem , Terapia a Laser , Estruturas Metalorgânicas/administração & dosagem , Infecções Estafilocócicas/terapia , Infecção dos Ferimentos/terapia , Administração Cutânea , Animais , Antibacterianos/química , Terapia Combinada/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ferrocianetos/administração & dosagem , Ferrocianetos/química , Humanos , Raios Infravermelhos/uso terapêutico , Masculino , Estruturas Metalorgânicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanopartículas/administração & dosagem , Nanopartículas/química , Ratos , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Infecção dos Ferimentos/microbiologia , Zinco/administração & dosagem , Zinco/química
5.
ACS Cent Sci ; 5(9): 1591-1601, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31572786

RESUMO

Herein, a core-shell dual metal-organic framework (MOF) heterointerface is synthesized. The Prussian blue (PB) MOF acts as a core for the growth of a porphyrin-doped MOF which is named PB@MOF. Porphyrins can significantly enhance the transfer of photoinspired electrons from PB and suppress the recombination of electrons and holes, thus enhancing the photocatalytic properties and consequently promoting the yields of singlet oxygen rapidly under 660 nm illumination. PB@MOF can exhibit a better photothermal conversion efficiency up to 29.9% under 808 nm near-infrared irradiation (NIR). The PB@MOF heterointerface can possess excellent antibacterial efficacies of 99.31% and 98.68% opposed to Staphylococcus aureus and Escherichia coli, separately, under the dual light illumination of 808 nm NIR and 660 nm red light for 10 min. Furthermore, the trace amount of Fe and Zr ions can trigger the immune system to favor wound healing, promising that PB@MOF achieves the rapid therapy of bacterial infected wounds and environmental disinfection.

6.
Biomater Sci ; 7(12): 5383-5387, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626246

RESUMO

Xerogels usually possess a stable structure and have a low swelling rate due to their inferior dynamics. Herein, a xerogel was synthesized by "imitative" click chemistry based on lipoic acid for picking up bacteria from wound sites, and thus accelerating tissue repair. The cross-linking structure of disulfide and thioether inside the xerogel not only exhibited good ductility and intrinsic self-healing performance, but also showed superior biocompatibility. The xerogel captured more than 60% of the bacteria Staphylococcus aureus via strong electrostatic adsorption in the colonies with a bacteria count of 106. In addition, this xerogel can stick to the skin in the form of patches in the wounds during therapy for wound healing and can be easily stripped from the skin after treatment, which makes it appropriate for the portable therapy of bacteria-infected wounds in emergency circumstances.

7.
Adv Sci (Weinh) ; 6(17): 1900599, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31508278

RESUMO

Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine-glycine-aspartic acid-cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron-sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near-infrared (NIR, λ = 700-1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.

8.
ACS Appl Mater Interfaces ; 11(37): 34364-34375, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31442020

RESUMO

In this study, a multifunctional hybrid coating composed of AgBr nanoparticles (AgBrNPs) and two-dimensional molybdenum sulfide (MoS2) nanosheets (AgBr@MoS2) was constructed on Ti implant materials using an in situ growth method for the first time. With 660 nm light and visible light irradiation, the electrons were rapidly excited from the valence band of MoS2 to its conduction band, at the same time, AgBrNPs was used as a photoelectric receiver, which exhibited an enhanced photocatalytic activity due to the rapid transfer of photoelectrons from MoS2 nanosheets to AgBrNPs and the suppression of the recombination of electron-hole pairs. This contributed to the rapid production of reactive oxygen species under 660 nm light irradiation, thus the AgBr@MoS2 system killed bacteria and degraded organic matter quickly and efficiently in a short time. Meanwhile, the AgBr@MoS2 system showed excellent stability due to the strong covalent binding between S and Ag in the system, thus preventing AgBrNPs from being reduced to metal Ag.


Assuntos
Antibacterianos , Bactérias/crescimento & desenvolvimento , Brometos , Desinfecção , Dissulfetos , Luz , Molibdênio , Nanopartículas/química , Compostos de Prata , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Brometos/química , Brometos/farmacologia , Linhagem Celular , Dissulfetos/química , Dissulfetos/farmacologia , Humanos , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Molibdênio/química , Molibdênio/farmacologia , Ratos , Ratos Sprague-Dawley , Compostos de Prata/química , Compostos de Prata/farmacologia
9.
Adv Healthc Mater ; 8(19): e1900835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464096

RESUMO

Bacterial infections often cause orthopedic surgery failures. It is hard for the immune system and antibiotics to clear bacteria adhered to implants after they form a mature biofilm, and a secondary surgery is required to remove the infected implants. To avoid this, a hybrid coating of Bi2 S3 @Ag3 PO4 /Ti is prepared to eliminate biofilm using near-infrared (NIR) light. Bi2 S3 nanorod (NR) arrays are prepared on titanium (Ti) implants through hydrothermal methods, and Ag3 PO4 nanoparticles (NPs) are loaded on Bi2 S3 NR arrays using a stepwise electrostatic adsorption strategy. The introduction of Ag3 PO4 NPs enhances the photocatalysis performances of Bi2 S3 , and the hybrid coating also exhibits good photothermal effects. After 808 nm light irradiation for 15 min, it shows superior bactericidal efficiency of 99.45% against Staphylococcus aureus, 99.74% against Escherichia coli in vitro, and 94.54% against S. aureus biofilm in vivo. Bi2 S3 @Ag3 PO4 /Ti also shows good cell viability compared to pure Ti. This NIR-activated-inorganic hybrid semiconductor heterojunction coating is biocompatible and could be employed to eliminate biofilm effectively, which makes it a very promising strategy for the surface modification of bone implant materials.

10.
ACS Nano ; 13(10): 11153-11167, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31425647

RESUMO

Patients often face the challenge of antibiotic-resistant bacterial infections and lengthy tissue reconstruction after surgery. Herein, human hair-melanosome derivatives (HHMs), comprising keratins and melanins, are developed using a simple "low-temperature alkali heat" method for potentially personalized therapy. The mulberry-shaped HHMs have an average width of ∼270 nm and an average length of ∼700 nm, and the negatively charged HHMs can absorb positively charged Lysozyme (Lyso) to form the HHMs-Lyso composites through electrostatic interaction. These naturally derived biodegradable nanostructures act as exogenous killers to eliminate methicillin-resistant Staphylococcus aureus (MRSA) infection with a high antibacterial efficacy (97.19 ± 2.39%) by synergistic action of photothermy and "Lyso-assisted anti-infection" in vivo. Additionally, HHMs also serve as endogenous regulators of collagen alpha chain proteins through the "protein digestion and absorption" signaling pathway to promote tissue reconstruction, which was confirmed by quantitative proteomic analysis in vivo. Notably, the 13 upregulated collagen alpha chain proteins in the extracellular matrix (ECM) after HHMs treatment demonstrated that keratin from HHMs in collagen-dependent regulatory processes serves as a notable contributor to augmented wound closure. The current paradigm of natural material-tissue interaction regulates the cell-ECM interaction by targeting cell signaling pathways to accelerate tissue repair. This work may provide insight into the protein-level pathways and the potential mechanisms involved in tissue repair.

11.
J Org Chem ; 84(16): 10221-10236, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31313581

RESUMO

Palladium-catalyzed arylation of unactivated ß-C(sp3)-H bonds in carboxylic acid derivatives with aryl iodides is described for the first time using 2-amino-5,6-difluorophenyl-1H-pyrazole as an efficient and readily removable directing group. Two fluoro groups are installed at the 5- and 6-position of the anilino moiety in 2-aminophenyl-1H-pyrazole, clearly enhancing the directing ability of the auxiliary. In addition, the protocol employs Cu(OAc)2/Ag3PO4 (1.2/0.3) as additives, evidently reducing the stoichiometric amount of expensive silver salts. Furthermore, this process exhibits high ß-site selectivity, compatibility with diverse substrates containing α-hydrogen atoms, and excellent functional group tolerance.

12.
J Hazard Mater ; 380: 120818, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31310928

RESUMO

Bacterial infection has become a serious public health challenge because the misuse of antibiotics worldwide has induced bacterial resistance and superbug occurrences, that is, no suitable antibiotics are available. Herein, we design a new infrared photocatalytic system on titanium (Ti) substrates, and it consists of gold (Au) nanorod-decorated bismuth tungstate (Bi2WO6) nanosheets (Au@Bi2WO6). The surface plasmon resonance (SPR) effect induced by near infrared (NIR) facilitates partial photo-induced electron transfer between Au and Bi2WO6, resulting in accelerated charge transmission and consequently hindering electron-hole recombination, which imparts high photocatalytic property to the coating. In addition, the superimposed SPR from both Au and Bi2WO6 can improve the photothermal effect of Au@Bi2WO6. As a result, when irradiated with 808 nm NIR for 15 min, this hybrid coating exhibits a superior antibacterial efficiency of 99.96% and 99.62% against Escherichia coli and Staphylococcus aureus, respectively, due to the synergistic effects of high yield of radical oxygen species and hyperthermia; this efficiency cannot be achieved by either Au-Ti or Bi2WO6-Ti alone. This platform exhibits a great potential for noninvasive disinfection without using antibiotics.

13.
Small ; 15(28): e1901020, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31148404

RESUMO

Oxygen evolution reaction (OER) is of great significance for hydrogen production via water electrolysis, which, however, demands development of highly active, durable, and cost-effective electrocatalysts in order to stride into a renewable energy era. Herein, highly efficient and long-term durable OER by coupling B and P into an amorphous porous NiFe-based electrocatalyst is reported, which possesses an amorphous porous metallic bulk structure and high corrosion resistance, and overcomes the issues associated with currently used catalyst nanomaterials. The PB codoping in the activated NiFePB (a-NiFePB) delocalizes both Fe and Ni at Fermi energy level and enhances p-d hybridization as simulated by density functional theory calculations. The harmonized electronic structure and unique porous framework of the a-NiFePB consequently improve the OER activity. The activated NiFePB thus exhibits an extraordinarily low overpotential of 197 mV for harvesting 10 mA cm-2 OER current density and 233 mV for reaching 100 mA cm-2 under chronopotentiometry condition, with the Tafel slope harmoniously conforming to 34 mV dec-1 . Impressive long-term stability of this new catalyst is evidenced by only limited activity decay after 1400 h operation at 100 mA cm-2 . This work strategically directs a way for heading up a promising energy conversion alternative.

14.
J Hazard Mater ; 377: 227-236, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31170571

RESUMO

Herein, a heterostructure based on MnO2 and g-C3N4 was constructed on the surface of metallic Ti implants, in which MnO2 favored the transfer and separation of free charges to enhance the photoconversion efficiency of g-C3N4 by 21.11%. Consequently, the yield of ROS was promoted significantly, which denatured protein and damaged DNA to kill bacteria efficiently. In addition, glutathione (GSH, l-γ-glutamyl-l-cysteinyl-glycine) defending oxidative stress in bacteria, was oxidized by MnO2 in the hybrid coating once the bacterial membrane was disrupted by ROS. Hence, after visible light irradiation for 20 min, MnO2/g-C3N4 coating exhibited superior disinfection efficacy of 99.96% and 99.26% against S. aureus and E. coli severally. This work provided a practical sterilization strategy about MnO2/g-C3N4 systems through the synergistic effects of enhanced photodynamic antibacterial therapy and oxidization effect of MnO2 with great biosafety, in which MnO2 enhanced the photocatalyst property of g-C3N4 to generate more ROS and deplete GSH to improve antibacterial efficiency. It will bring more insight into rapid and highly effective disinfection and antibacterial strategy without using traditional high-temperature, ultraviolet ray and antibiotics that cause side-effects.

15.
Small ; 15(22): e1900322, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31021489

RESUMO

One of the most difficult challenges in the biomedical field is bacterial infection, which causes tremendous harm to human health. In this work, an injectable hydrogel is synthesized through rapid assembly of dopamine (DA) and folic acid (FA) cross-linked by transition metal ions (TMIs, i.e., Zn2+ ), which was named as DFT-hydrogel. Both the two carboxyl groups in the FA molecule and catechol in polydopamine (PDA) easily chelates Zn2+ to form metal-ligand coordination, thereby allowing this injectable hydrogel to match the shapes of wounds. In addition, PDA in the hydrogel coated around carbon quantum dot-decorated ZnO (C/ZnO) nanoparticles (NPs) to rapidly generate reactive oxygen species (ROS) and heat under illumination with 660 and 808 nm light, endows this hybrid hydrogel with great antibacterial efficacy against Staphylococcus aureus (S. aureus, typical Gram-positive bacteria) and Escherichia coli (E. coli, typical Gram-negative bacteria). The antibacterial efficacy of the prepared DFT-C/ZnO-hydrogel against S. aureus and E. coli under dual-light irradiation is 99.9%. Importantly, the hydrogels release zinc ions over 12 days, resulting in a sustained antimicrobial effect and promoted fibroblast growth. Thus, this hybrid hydrogel exhibits great potential for the reconstruction of bacteria-infected tissues, especially exposed wounds.

16.
J Cancer ; 10(6): 1503-1510, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031860

RESUMO

Objectives: LncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) is a newly discovered long non-coding RNA that aberrantly up-regulates and holds prognostic value in various tumors. The aim of the review and meta-analysis is to assess its prognostic potential and functions in malignant tumors. Materials and methods: PubMed, PMC, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database were carefully searched for articles published as of Jan. 1, 2018. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of lncRNA MVIH using Stata 12.0 software. Results: Six original studies including 830 cancer patients were ultimately enrolled in this meta-analysis. The pooled results showed that elevated lncRNA MVIH expression was significantly correlated with unfavorable OS (HR=2.17, 95% CI: 1.58-2.76, p < 0.001) and RFS/DFS/PFS (HR=2.21, 95% CI: 1.54-2.87, p < 0.001) in cancer patients. Additionally, high expression of lncRNA MVIH was related to positive lymph node metastasis (OR = 3.04, 95% CI: 1.37-6.75, p = 0.006) and advanced clinical stage (OR = 2.52, 95% CI: 1.68-3.79, p < 0.001). Conclusions: LncRNA MVIH over-expression was associated with poor clinical outcomes in multiple cancer types. More studies are warranted to verify and strengthen the clinical value of lncRNA MVIH in human cancers.

17.
ACS Appl Mater Interfaces ; 11(19): 17902-17914, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31013044

RESUMO

Bacterial infection is still a ticklish clinical challenge even though some advanced antibacterial materials and techniques have been put forward. This work reports that rapid and effective antibacterial performance is achieved by the synergistic local photothermal and photodynamic therapy (PTDT). Within 10 min of light irradiation, both Escherichia coli and Staphylococcus aureus are almost completely eliminated by the action of photothermy (52.1 °C) and limited reactive oxygen species (ROS), the corresponding bacterial killing efficiencies are 99.91 and 99.97%, respectively, which are far higher than single modal therapy, i.e., photothermal therapy or photodynamic therapy with antibacterial efficacy of 50 or 70%, respectively. The mechanism is that bacterial membrane permeation is increased by PTDT because photothermy shows more severe impact only on E. coli by destroying the outmost bacterial panniculus, whereas the inner panniculus of the two kinds of bacteria is more sensitive to ROS. Hence, ROS penetrates the bacterial membrane more easily, and meanwhile, the proteins in the bacteria are severely lost after the bacterial membrane disruption, which leads to bacterial death. In vivo results reveal that rapid and effective sterilization is an important process to accelerate wound healing, and the traumas on the rats' backbones heal well within 12 days by PTDT. Furthermore, the PTDT is friendly to major organs of rats during the therapeutic process. Therefore, the synergistic therapy system can be a safe therapeutic system for clinical sterilization with great potential. More importantly, the antibacterial mechanism presented in this work has great guiding significance for the design of other advanced antibacterial systems and techniques.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/terapia , Fotoquimioterapia , Espécies Reativas de Oxigênio/química , Animais , Antibacterianos/química , Infecções Bacterianas/microbiologia , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Ratos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Cicatrização/efeitos dos fármacos
18.
ACS Appl Mater Interfaces ; 11(16): 15014-15027, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30933472

RESUMO

A bacterial infection on the surface of medical apparatus and instruments as well as artificial implants is threatening human health greatly. Antibiotics and traditional bacterial-killing agents, even silver nanoparticles, can induce bacterial resistance during long-term interaction with bacteria. Hence, rapid surface sterilization and prevention of bacterial infection in the long term are urgent for biomedical devices, especially for artificial implant materials. Herein, a hybridized chitosan (CS), silver nanoparticles (AgNPs), and MnO2 nanosheets coating was designed on the surface of titanium plates, which can ensure the implants a rapid and highly effective antibacterial efficacy of 99.00% against Staphylococcus aureus ( S. aureus) and 99.25% against Escherichia coli ( E. coli) within 20 min of 808 nm near-infrared light (NIR) irradiation. The exogenous NIR irradiation can trigger the MnO2 nanosheets to produce enough hyperthermia within 10 min, which can combine with a low concentration of prereleased Ag+ from the coating to achieve superior antimicrobial efficacy through synergistic effects. In contrast, either prereleased Ag ions or a photothermal effect alone can achieve much lower antibacterial efficiency under the same concentration, i.e., 24.00% and 30.01% for the former and 30.00% and 42.54% for the later toward S. aureus and E. coli, respectively. The possible cytotoxicity of coatings could be eliminated owing to the low concentration of AgNPs and chitosan encapsulation. Thus, the novel bifunctional coating Ag/CS@MnO2 can exhibit great potential in deep site disinfection of Ti implants through the synergy of prereleased Ag ions and a photothermal effect within a short time.


Assuntos
Quitosana , Materiais Revestidos Biocompatíveis , Desinfecção , Escherichia coli/crescimento & desenvolvimento , Raios Infravermelhos , Compostos de Manganês , Nanopartículas/química , Óxidos , Prata , Staphylococcus aureus/crescimento & desenvolvimento , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Camundongos , Células NIH 3T3 , Óxidos/química , Óxidos/farmacologia , Prata/química , Prata/farmacologia
19.
Biomater Sci ; 7(4): 1675-1685, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30742145

RESUMO

Accelerating the healing of bone fractures by local delivery of growth factors possessing osteoinductive activity has been extensively demonstrated. Unfortunately, for some complex clinical fractures, such as osteoporotic vertebral compression fracture, it is not possible to adopt such a strategy because of access restrictions. Systemic administration of growth factors is considered to be an appropriate alternative method due to its easy operability and precise spatiotemporal compatibility at fracture sites. But this therapy method was hampered by the poor in vivo stability, inefficient distribution at the fracture site and potential side effects of growth factors. To address these challenges, we conceived a systemic delivery platform of growth factors based on nanocapsules, taking advantage of the unique physiological character of bone fracture, i.e., the malformed blood vessels and the over-expression of matrix metalloproteinases (MMPs). In this work, bone morphogenetic protein-2 (BMP-2), 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and the bisacryloylated VPLGVRTK peptide were respectively used as the model growth factor, monomer, and MMP-cleavable crosslinker. Nanocapsules were formed by in situ free radical polymerization on the surface of BMP-2 with MPC and peptides. The structure and function of BMP-2 were well maintained during the preparation process. BMP-2 nanocapsules (n(BMP-2)) were of uniform small size (∼30 nm) possessing a long circulation time (half-life is ∼48 h) and could be passively targeted to the fracture site through malformed blood vessels after systemic administration. Once accumulated at the fracture site, the shells of nanocapsules could be degraded by MMP and thus BMP-2 was released. Animal experiments proved that n(BMP-2) showed a better ability of bone repair than native BMP-2. In addition, n(BMP-2) showed a much lower inflammatory irritation. The results demonstrated that the systemic administration of growth factor nanocapsules could enhance their in vivo stability and fracture site delivery efficiency, realizing the efficient repair of a bone fracture. This rational delivery system may expand the bone repair types which can be administered with growth factors. Furthermore, the concept of taking advantage of the malformed vascular structure to deliver drugs potentially inspires researchers for the therapy of other diseases, especially sudden disease (such as cerebral hemorrhage).


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Regeneração Óssea , Metaloproteinase 9 da Matriz/metabolismo , Nanocápsulas/uso terapêutico , Fraturas da Tíbia/terapia , Animais , Proteína Morfogenética Óssea 2/administração & dosagem , Linhagem Celular , Modelos Animais de Doenças , Humanos , Metaloproteinase 9 da Matriz/administração & dosagem , Camundongos , Nanocápsulas/química , Osteogênese , Tamanho da Partícula , Células RAW 264.7 , Ratos , Fraturas da Tíbia/metabolismo , Fraturas da Tíbia/patologia
20.
Biomater Sci ; 7(4): 1437-1447, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30666993

RESUMO

Implant materials are prone to bacterial infections and cause serious consequences, while traditional antibiotic therapy has a long treatment cycle and even causes bacterial resistance. In this work, a photothermal therapy (PTT) assisted drug release system has been developed on the implant surface for in situ rapid disinfection under 808 nm light irradiation within a short time, in which gentamicin (Gent) is loaded by polyethylene glycol (PEG) modified molybdenum disulfide (MoS2) on Ti surface, and then encapsulated with chitosan (CS) (CS/Gent/PEG/MoS2-Ti). The hyperthermia produced by the coatings irradiated by 808 nm near-infrared (NIR) light can not only accelerate the local release of Gent, but also reduce the activity of bacteria, which makes it easy for these locally released drugs to enter the interior of the bacteria to inhibit the protein synthesis and destroy the cell membrane. When maintained at 50 °C for 5 min under NIR irradiation, this system can achieve an antibacterial efficacy of 99.93% and 99.19% against Escherichia coli and Staphylococcus aureus, respectively. By contrast, even after treatment for 120 min, only a 93.79% antibacterial ratio can be obtained for Gent alone. This is because hyperthermia produced from the coatings during irradiation can assist antibiotics in killing bacteria in a short time. Even under a low dose of 2 µg mL-1, the photothermal effect assisted gentamicin can achieve an antibacterial efficacy of 96.86% within 5 min. In vitro cell culture shows that the modified surface can facilitate cell adhesion, spreading and proliferation. The 7 day subcutaneous infection model confirms that the prepared surface system can exhibit a much faster sterilization and tissue reconstruction than the control group with light assistance. Compared with the traditional drug release system, this photothermy controlled drug-loaded implant surface system can not only provide rapid and high-efficiency in situ sterilization, but also offer long-term prevention of local bacterial infection.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Gentamicinas/farmacologia , Fototerapia , Staphylococcus aureus/efeitos dos fármacos , Temperatura Ambiente , Animais , Antibacterianos/síntese química , Antibacterianos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Dissulfetos/química , Dissulfetos/farmacologia , Gentamicinas/síntese química , Gentamicinas/química , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Molibdênio/química , Molibdênio/farmacologia , Células NIH 3T3 , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/tratamento farmacológico , Propriedades de Superfície , Titânio/química , Titânio/farmacologia
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