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Acta Biomaterialia Jun 2022Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic...
Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic wounds possess an elevated local pH of 8.9 and developed pH-sensitive silica nanoparticles (SiNPs) to achieve a targeted drug release on alkaline wounds and optimized drug utility. Chlorhexidine (CHX), a disinfectant and antiseptic, was loaded into SiNPs as the model drug. The loaded CHX displayed a release 4 - 5 fold higher at pH 8.0 and 8.5 than at pH 6.5, 7.0 and 7.4. CHX-SiNPs furthermore exhibited a distinctive antibacterial activity at pH 8.0 and 8.5 against both Gram-negative and -positive bacterial pathogens, while no cytotoxicity was found according to cell viability analysis. The CHX-SiNPs were further formulated into alginate hydrogels to allow ease of use. The antibacterial efficacy of CHX-SiNPs was then studied with artificial wounds on ex vivo human skin. Treatment with CHX-SiNPs enabled nearly a 4-lg reduction of the viable bacterial cells, and the alginate formulated CHX-SiNPs led to almost a 3-lg reduction compared to the negative controls. The obtained results demonstrated that CHX-SiNPs are capable of efficient pH-triggered drug release, leading to high antibacterial efficacy. Moreover, CHX-SiNPs enlighten clinic potential towards the treatment of chronic wound infections. STATEMENT OF SIGNIFICANCE: A platform for controlled drug release at a relatively high pH value i.e., over 8, was established by tuning the physical structures of silica nanoparticles (SiNPs). Incorporation of chlorhexidine, an antimicrobial agent, into the fabricated SiNPs allowed a distinctive inhibition of bacterial growth at alkaline pHs, but not at acidic pHs. The efficacy of the SiNPs loaded with chlorhexidine in treating wound infections was further validated by utilizing ex vivo human skin samples. The presented work demonstrates clinic potential of employing alkaline pH as a non-invasive stimulus to achieve on-demand delivery of antimicrobials through SiNPs, showcasing a valuable approach to treating bacterial infections on chronic wounds.
Topics: Alginates; Anti-Bacterial Agents; Chlorhexidine; Humans; Nanoparticles; Silicon Dioxide; Wound Infection
PubMed: 35417797
DOI: 10.1016/j.actbio.2022.04.009 -
Antiviral Research Feb 2023In the past decade, interest in nanoparticles for clinical indications has been steadily gaining traction. Most recently, Lipid Nanoparticles (LNP) have been used... (Review)
Review
In the past decade, interest in nanoparticles for clinical indications has been steadily gaining traction. Most recently, Lipid Nanoparticles (LNP) have been used successfully to construct the SARS-CoV-2 mRNA vaccines for rapid pandemic response. Similarly, silica is another nanomaterial which holds much potential to create nanomedicines against pathogens of interest. One major advantage of silica-based nanoparticles is its crystalline and highly ordered structure, which can be specifically tuned to achieve the desired properties needed for clinical applications. Increasingly, clinical research has shown the potential of silica nanoparticles not only as an antiviral, but also its ability as a delivery system for antiviral small molecules and vaccines against viruses. Silica has an excellent biosafety profile and has been tested in several early phase clinical trials since 2012, demonstrating good tolerability and minimal reported side effects. In this review, we discuss the clinical development of silica nanoparticles to date and identify the gaps and potential pitfalls in its path to clinical translation.
Topics: Humans; Silicon Dioxide; COVID-19; SARS-CoV-2; Viruses; Antiviral Agents; Nanoparticles
PubMed: 36566118
DOI: 10.1016/j.antiviral.2022.105488 -
Environmental Health Perspectives Dec 1994Exposure to crystalline silica can result in damage to the lung parenchyma and scarring that can lead to fibrosis. Pulmonary damage may be the direct consequence of... (Review)
Review
Exposure to crystalline silica can result in damage to the lung parenchyma and scarring that can lead to fibrosis. Pulmonary damage may be the direct consequence of toxic interaction between quartz particles and cell membranes, or it may be due to silica-induced production of oxidant species by pulmonary phagocytes, that in turn overwhelms pulmonary antioxidant systems and causes lung injury. Data indicate that grinding or fracturing quartz particles breaks Si-O bonds and generates .Si and Si-O. radicals on the surface of the cleavage planes. Upon contact with water, these silica-based radicals can generate hydroxyl radicals (.OH). These surface radicals decay as fractured silica dust is aged. Freshly fractured quartz is significantly more potent than aged silica in directly causing lipid peroxidation, membrane damage, and cell death. Furthermore, freshly ground silica is a more potent stimulant of alveolar macrophages than aged silica. This silica-induced activation results in the production of superoxide (O2-), hydrogen peroxide (H2O2), nitric oxide (NO.), and other oxidant species that can damage lung cells. Tetrandrine, an herbal medicine that exhibits antifibrotic activity in rat models of silicosis, effectively blocks the ability of quartz to stimulate oxidant release from pulmonary phagocytes.
Topics: Alkaloids; Animals; Benzylisoquinolines; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Free Radicals; Lung Diseases; Macrophages, Alveolar; Rats; Reactive Oxygen Species; Silicon Dioxide
PubMed: 7705309
DOI: 10.1289/ehp.94102s1065 -
International Journal of Molecular... Feb 2024Diatom biosilica is an important natural source of porous silica, with three-dimensional ordered and nanopatterned structures referred to as frustules. The unique... (Review)
Review
Diatom biosilica is an important natural source of porous silica, with three-dimensional ordered and nanopatterned structures referred to as frustules. The unique features of diatom frustules, such as their high specific surface area, thermal stability, biocompatibility, and adaptable surface chemistry, render diatoms valuable materials for high value-added applications. These attributes make diatoms an exceptional cost-effective raw material for industrial use. The functionalization of diatom biosilica surface improves its biophysical properties and increases the potential applications. This review focuses on the potential uses of diatom biosilica including traditional approaches and recent progress in biomedical applications. Not only well-studied drug delivery systems but also promising uses on bone regeneration and wound healing are covered. Furthermore, considerable aspects and possible future directions for the use of diatom biosilica materials are proposed to develop biomedical applications and merit further exploration.
Topics: Diatoms; Biomimetics; Drug Delivery Systems; Silicon Dioxide; Porosity
PubMed: 38396701
DOI: 10.3390/ijms25042023 -
Molecules (Basel, Switzerland) Aug 2020We conducted systemic assessments on the toxicity of silicon dioxide (SiO) and titanium dioxide (TiO) nanoparticles using different forms of normal colon cells...
We conducted systemic assessments on the toxicity of silicon dioxide (SiO) and titanium dioxide (TiO) nanoparticles using different forms of normal colon cells (CCD-18Co), in vivo and in human colon organoids. The in vivo acute oral toxicity data showed that the LD values are greater than 2000 mg/kg for both the SiO and TiO nanoparticles; however, the SiO and TiO nanoparticles induced cytotoxicity in two-dimensional CCD-18Co cells and three-dimensional CCD-18Co spheroids and human colon organoids, with IC values of 0.6, 0.8 and 0.3 mM for SiO and 2.5, 1.1 and 12.5 mM for TiO nanoparticles, respectively. The data suggest that, when SiO and TiO are in nanoparticle form, cytotoxicity is induced; thus, care should be taken with these materials.
Topics: Animals; Cell Line; Colon; Humans; Mice; Mice, Inbred ICR; Nanoparticles; Organoids; Silicon Dioxide; Titanium; Toxicity Tests
PubMed: 32784677
DOI: 10.3390/molecules25163594 -
Nanomedicine (London, England) Dec 2013Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle, have recently gained increasing interest owing... (Review)
Review
Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle, have recently gained increasing interest owing to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in the engineering of functionalized HMSNs (i.e., f-HMSNs), with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, PET, MRI and ultrasound imaging in preclinical studies. Finally, we discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy.
Topics: Animals; Humans; Magnetic Resonance Imaging; Nanoparticles; Neoplasms; Optical Imaging; Porosity; Positron-Emission Tomography; Silicon Dioxide; Ultrasonography
PubMed: 24279491
DOI: 10.2217/nnm.13.177 -
Wiley Interdisciplinary Reviews.... Jul 2016The management of regional lymph nodes in patients with melanoma has undergone a significant paradigm shift over the past several decades, transitioning from the use of... (Review)
Review
The management of regional lymph nodes in patients with melanoma has undergone a significant paradigm shift over the past several decades, transitioning from the use of more aggressive surgical approaches, such as lymph node basin dissection, to the application of minimally invasive sentinel lymph node (SLN) biopsy methods to detect the presence of nodal micrometastases. SLN biopsy has enabled reliable, highly accurate, and low-morbidity staging of regional lymph nodes in early stage melanoma as a means of guiding treatment decisions and improving patient outcomes. The accurate identification and staging of lymph nodes is an important prognostic factor, identifying those patients for whom the expected benefits of nodal resection outweigh attendant surgical risks. However, currently used standard-of-care technologies for SLN detection are associated with significant limitations. This has fueled the development of clinically promising platforms that can serve as intraoperative visualization tools to aid accurate and specific determination of tumor-bearing lymph nodes, map cancer-promoting biological properties at the cellular/molecular levels, and delineate nodes from adjacent critical structures. Among a number of promising cancer-imaging probes that might facilitate achievement of these ends is a first-in-kind ultrasmall tumor-targeting inorganic (silica) nanoparticle, designed to overcome translational challenges. The rationale driving these considerations and the application of this platform as an intraoperative treatment tool for guiding resection of cancerous lymph nodes is discussed and presented within the context of alternative imaging technologies. WIREs Nanomed Nanobiotechnol 2016, 8:535-553. doi: 10.1002/wnan.1380 For further resources related to this article, please visit the WIREs website.
Topics: Humans; Lymphatic Metastasis; Molecular Imaging; Nanomedicine; Nanoparticles; Sentinel Lymph Node; Silicon Dioxide
PubMed: 26663853
DOI: 10.1002/wnan.1380 -
The FEBS Journal May 2012Owing to their physical and chemical properties, inorganic functional materials have tremendous impacts on key technologies such as energy generation and storage,... (Review)
Review
Owing to their physical and chemical properties, inorganic functional materials have tremendous impacts on key technologies such as energy generation and storage, information, medicine, and automotive engineering. Nature, on the other hand, provides evolution-optimized processes, which lead to multifunctional inorganic-bio-organic materials with complex structures. Their formation occurs under physiological conditions, and is goverened by a combination of highly regulated biological processes and intrinsic chemical properties. Nevertheless, insights into the molecular mechanisms of biomineralization open up promising perspectives for bioinspired and biomimetic design and the development of inorganic-bio-organic multifunctional hybrids. Therefore, biomimetic approaches may disclose new synthetic routes under ambient conditions by integrating the concept of gene-regulated biomineralization principles. The skeletal structures of marine sponges provide an interesting example of biosilicification via enzymatically controlled and gene-regulated silica metabolism. Spicule formation is initiated intracellularly by a fine-tuned genetic mechanism, which involves silica deposition in vesicles (silicassomes) under the control of the enzyme silicatein, which has both catalytic and templating functions. In this review, we place an emphasis on the fabrication of biologically inspired materials with silicatein as a biocatalyst.
Topics: Animals; Biomimetic Materials; Cathepsins; Enzymes; Nanostructures; Porifera; Silicon Dioxide
PubMed: 22510103
DOI: 10.1111/j.1742-4658.2012.08584.x -
Scientific Reports Jul 2016Hardware implementation of artificial neural networks facilitates real-time parallel processing of massive data sets. Optical neural networks offer low-volume 3D...
Hardware implementation of artificial neural networks facilitates real-time parallel processing of massive data sets. Optical neural networks offer low-volume 3D connectivity together with large bandwidth and minimal heat production in contrast to electronic implementation. Here, we present a conceptual design for in-fiber optical neural networks. Neurons and synapses are realized as individual silica cores in a multi-core fiber. Optical signals are transferred transversely between cores by means of optical coupling. Pump driven amplification in erbium-doped cores mimics synaptic interactions. We simulated three-layered feed-forward neural networks and explored their capabilities. Simulations suggest that networks can differentiate between given inputs depending on specific configurations of amplification; this implies classification and learning capabilities. Finally, we tested experimentally our basic neuronal elements using fibers, couplers, and amplifiers, and demonstrated that this configuration implements a neuron-like function. Therefore, devices similar to our proposed multi-core fiber could potentially serve as building blocks for future large-scale small-volume optical artificial neural networks.
Topics: Computer Systems; Equipment Design; Fiber Optic Technology; Neural Networks, Computer; Optical Fibers; Silicon Dioxide
PubMed: 27383911
DOI: 10.1038/srep29080 -
Frontiers in Public Health 2023Despite of growing evidence linking silica nanoparticles (SiNPs), one of the global-top-three-produced and -used nanoparticle (NP), to human health risks, there remain...
INTRODUCTION
Despite of growing evidence linking silica nanoparticles (SiNPs), one of the global-top-three-produced and -used nanoparticle (NP), to human health risks, there remain many knowledge gaps over the adverse effects of SiNPs exposure on cardiovascular system and the underlying molecular mechanisms.
METHODS
In this study, the ferroptotic effects of SiNPs (20 nm; 0, 25, 50, and 100 μg/mL) on human umbilical vein endothelial cells (HUVECs) and the possible molecular mechanism were studied with the corresponding biochemical and molecular biology assays.
RESULTS AND DISCUSSION
The results showed that at the tested concentrations, SiNPs could decrease HUVEC viability, but the deferoxamine mesylate (an iron ion chelator) might rescue this reduction of cell viability. Also, increased levels of intracellular reactive oxygen species and enhanced mRNA expression of lipid oxidation enzymes (ACSL4 and LPCAT3) with increase in lipid peroxidation (malondialdehyde), but decreased ratios of intracellular GSH/total-GSH and mitochondrial membrane potential as well as reduced enzymatic activities of anti-oxidative enzymes (CAT, SOD, and GSH-PX), were found in the SiNPs-treated HUVECs. Meanwhile, increase in p38 protein phosphorylation and decrease in NrF2 protein phosphorylation with reduced mRNA expressions of downstream anti-oxidative enzyme genes (CAT, SOD1, GSH-PX, and GPX4) was identified in the SiNPs-exposed HUVECs. These data indicated that SiNPs exposure might induce ferroptosis in HUVECs p38 inhibiting NrF2 pathway. Ferroptosis of HUVECs will become a useful biomarker for assessing the cardiovascular health risks of environmental contaminants.
Topics: Humans; Human Umbilical Vein Endothelial Cells; NF-E2-Related Factor 2; Ferroptosis; Silicon Dioxide; Nanoparticles; RNA, Messenger
PubMed: 36844840
DOI: 10.3389/fpubh.2023.1024130