查看更多>>摘要：Photothermal therapy (PTT) is a promising strategy for antimicrobial therapy. However, the application of PTT to treat bacterial infections remains a challenge as the high temperature required for bacterial elimination can partly damage healthy tissues. Selecting the appropriate treatment temperature is therefore a key factor for PTT. In this work, we designed a near-infrared/pH dual stimuli-responsive activated procedural antibacterial system based on zeolitic imidazolate framework-8 (ZIF-8), which was bottom-up synthesized and utilized to encapsulate both Pd-Cu nanoalloy (PC) and the antibiotic amoxicillin (AMO). This procedural antibacterial therapy comprises chemotherapy (CT) and PTT. The former disrupts the bacterial cell wall by releasing AMO in an acidic environment, which depends on the sensitive response of ZIF-8 to pH value change. With the progression in time, the AMO release rate decreased gradually. The latter can then significantly stimulate drug release and further complete the antibacterial effect. This impactful attack consisted of two waves that constitute the procedural therapy for bacterial infection. Accordingly, the treatment temperature required for antibacterial therapy can be significantly lowered under this mode of treatment. This antibacterial system has a significant therapeutic effect on planktonic bacteria (G(+)/G(-)) and their biofilms and also has good biocompatibility; thus, it provides a promising strategy to develop an effective and safe treatment against bacterial infections. Statement of Significance We have developed a near infrared/pH dual stimuli-responsive activated procedural antibacterial system that combines enhanced antibiotic delivery with photothermal therapy and has highly efficient antimicrobial activity. The antibacterial effect of this therapy was based on two mechanisms of action: chemotherapy, in which the bacterial cell wall was first destroyed, followed by photothermal therapy. After exposure to irradiation with an 808 nm laser, the inhibition rates were 99.8% and 99.1% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the clearance rates for their established biofilms were 75.3% and 74.8%, respectively. Thus, this procedural antibacterial therapy has shown great potentiality for use in the photothermal therapy of bacterial infectious diseases, including biofilm elimination. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Impressive developments have been achieved with the use of zeolitic imidazolate framework-8 (ZIF-8) as nanocarriers for tumor theranostics in recent decades by incorporating imaging agents and therapeutic drugs within ZIF-8. However, the simultaneous immobilization of hydrophilic and hydrophobic functional molecules into ZIF-8 nanoparticles in water or organic solvents still presents a daunting challenge. Herein, we developed a new synthesis/encapsulation two-in-one (denoted as one-pot) approach to synthesize uniform dextran-modified Cy5.5&ICG@ZIF-8-Dex nanoparticles in DMSO/H2O solvent mixtures, which en-abled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hydrophobic cyanine-5.5 (Cy5.5) during the same step. It was confirmed that the one-pot approach in this mixed solvents facilitated the loading of ICG and Cy5.5 molecules. Moreover, the encapsulation of Cy5.5 and ICG within ZIF-8 nanoparticles endowed them with fluorescence imaging capability and photothermal conversion ca-pacity, respectively. The in vivo near-infrared (NIR) fluorescent images of A549-bearing mice injected with Cy5.5&ICG@ZIF-8-Dex demonstrated sufficient accumulations of Cy5.5 at tumor sites due to the enhanced permeability and retention effect. Most impressively, the fluorescent intensity of Cy5.5&ICG@ZIF-8-Dex at tumor site was approximately 40-fold higher than that of free Cy5.5. Additionally, the results of in vivo infrared imaging and photothermal therapy of Cy5.5&ICG@ZIF-8-Dex showed enhanced therapeutic effi-ciency in comparison with free ICG, further confirming its tumor-targeting capability and photothermal capacity. Therefore, this multifunctional system based on ZIF-8 nanocarriers offered a potential nanoplat-form for tumor-targeting theranostics, thus broadening the synthesis and applications of ZIF-8 composite nanoparticles for NIR fluorescence imaging and photothermal therapy in the biomedical field. Statement of significance Simultaneous immobilization of hydrophilic and hydrophobic molecules into ZIF-8 nanoparticles still re-mains a daunting challenge. Therefore, we have developed a new synthesis/encapsulation two-in-one approach to synthesize uniform Cy5.5&ICG@ZIF-8-Dex composite nanoparticles in DMSO/H2O solvent mixtures, which enabled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hy-drophobic cyanine-5.5 (Cy5.5) functional molecules during a single step. The results showed that the co-loading of Cy5.5 and ICG within the ZIF-8 nanoparticles endowed them with a remarkable fluores-cence imaging capability and photothermal conversion capacity. Based on their enhanced convenience and efficacy to simultaneously encapsulate hydrophilic and hydrophobic molecules, the multifunctional nanocarriers that were prepared in the DMSO/H2O mixed solvents provide a potential nanoplatform to-ward fluorescence imaging and photothermal therapy for tumor theranostics. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Considered as some of the most devastating complications, Cutibacterium acnes ( C. acnes)-related os-teomyelitis are among the hardest infections to diagnose and treat. Mesenchymal stem cells (MSCs) se-crete number of immunomodulatory and antimicrobial soluble factors, making them an attractive treat-ment for bacterial infection. In this study, we examined MSCs/C. acnes interaction and analyzed the sub-sequent MSCs and bacteria's behaviors. Human bone marrow-derived MSCs were infected by C. acnes clinical strain harvested from non-infected bone site. Following 3 h of interaction, around 4% of bacte-ria were found in the intracellular compartment. Infected MSCs increased the secretion of prostaglandin E2 and indolamine 2,3 dioxygenase immunomodulatory mediators. Viable intracellular bacteria analyzed by infrared spectroscopy and atomic force microscopy revealed deep modifications in the wall features. In comparison with unchallenged bacteria, the viable intracellular bacteria showed (i) an increase in biofilm formation on orthopaedical-based materials, (ii) an increase in the invasiveness of osteoblasts and (iii) persistence in macrophage, suggesting the acquisition of virulence factors. Overall, these re-sults showed a direct impact of C. acnes on bone marrow-derived MSCs, suggesting that blocking the C. acnes/MSCs interactions may represent an important new approach to manage chronic osteomyelitis infections. Statement of significance The interaction of bone commensal C. acnes with bone marrow mesenchymal stem cells induces modifica-tions in C. acnes wall characteristics. These bacteria increased (i) the biofilm formation on orthopaedical-based materials, (ii) the invasiveness of bone forming cells and (iii) the resistance to macrophage clear-ance through the modification of the wall nano-features and/or the increase in catalase production. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Definitive prevention of inflammatory osteolysis around peri-implant bone tissue remains unestablished. M1 macrophages play a key role in the host defense against inflammatory osteolysis, and their polariza-tion depends on cell shape. Macrophage polarization is controlled by environmental stimuli, particularly physicochemical cues and hence titanium nanosurface might tune macrophage polarization and function. This study determined whether titanium nanosurfaces with anisotropically patterned nanospikes regu-lates macrophage polarization for inhibiting osteoclast differentiation of osteoclast precursors. Alkaline-etching treatment with different protocols created two types of titanium nanosurfaces that had anisotrop-ically patterned nanospikes with high or low distribution density, together with superhydrophilicity and the presence of hydroxyl groups. J774A.1 cells (mouse macrophage-like cell line), cultured on both ti-tanium nanosurfaces, exhibited truly circulated shapes and highly expressed M1, but less M2, mark-ers, without loss of viability. M1-like polarization of macrophages on both titanium nanosurfaces was independent of protein-mediated ligand stimulation or titanium surface hydrophilic or chemical sta-tus. In contrast, other smooth or micro-roughened titanium surfaces with little or no nanospikes did not activate macrophages under any culture conditions. Macrophage culture supernatants on both ti-tanium nanosurfaces inhibited osteoclast differentiation of RAW264.7 cells (mouse osteoclast precursor cell line), even when co-incubated with osteoclast differentiation factors. The inhibitory effects on osteo-clast differentiation tended to be higher in macrophages cultured on titanium nanosurfaces with denser nanospikes. These results showed that titanium nanosurfaces with anisotropically patterned nanospikes tune macrophage polarization for inhibiting osteoclast differentiation of osteoclast precursors, with nan-otopographic cues rather than other physicochemical properties.
查看更多>>摘要：Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions. The efficacy of this treatment was assessed by comparing standard and surface-treated Nitinol disks and braids, equivalent to flow diverters. Static and dynamic (Chandler loop) blood incubation tests showed a drastic reduction of thrombus formation on treated devices. Surface chemistry and proteomic analysis indicated a key role of phosphate and calcium ions in steering blood protein adsorption and avoiding coagulation cascade activation and platelet adhesion. A good endothelialization of the surface confirmed the biocompatibility of the treated surface. Statement of significance Titanium alloys such as Nitinol are biocompatible and show favorable mechanical properties, which led to their widespread use in medical implants. However, in contact with blood their surface triggers the activation of the intrinsic coagulation cascade, which may result in catastrophic thrombotic events. The presented results showed that a phosphate functionalization of the titanium oxide surface suppresses the activation of both coagulation cascade and platelets, avoiding the subsequent formation of a blood clot. This novel approach has therefore a great potential for mitigating the risks associated to either thrombosis or bleeding complications (due to systemic anticoagulation) in patients with cardiovascular implants. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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