共查询到20条相似文献，搜索用时 0 毫秒
1.
2.
Julia Blechinger Alexander T. Bauer Adriano A. Torrano Christian Gorzelanny Christoph Bräuchle Stefan W. Schneider 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(23):3970-3980
In this study, it is shown that the cytotoxic response of cells as well as the uptake kinetics of nanoparticles (NPs) is cell type dependent. We use silica NPs with a diameter of 310 nm labeled with perylene dye and 304 nm unlabeled particles to evaluate cell type‐dependent uptake and cytotoxicity on human vascular endothelial cells (HUVEC) and cancer cells derived from the cervix carcinoma (HeLa). Besides their size, the particles are characterized concerning homogeneity of the labeling and their zeta potential. The cellular uptake of the labeled NPs is quantified by imaging the cells via confocal microscopy in a time‐dependent manner, with subsequent image analysis via a custom‐made and freely available digital method, Particle_in_Cell‐3D. We find that within the first 4 h of interaction, the uptake of silica NPs into the cytoplasm is up to 10 times more efficient in HUVEC than in HeLa cells. Interestingly, after 10 or 24 h of interaction, the number of intracellular particles for HeLa cells by far surpasses the one for HUVEC. Inhibitor studies show that these endothelial cells internalize 310 nm SiO2 NPs via the clathrin‐dependent pathway. Remarkably, the differences in the amount of taken up NPs are not directly reflected by the metabolic activity and membrane integrity of the individual cell types. Interaction with NPs leads to a concentration‐dependent decrease in mitochondrial activity and an increase in membrane leakage for HUVEC, whereas HeLa cells show only a reduced mitochondrial activity and no membrane leakage. In addition, silica NPs lead to HUVEC cell death while HeLa cells survive. These findings indicate that HUVEC are more sensitive than HeLa cells upon silica NP exposure. 相似文献
3.
Serious side effects to surrounding normal tissues and unsatisfactory therapeutic efficacy hamper the further clinic applications of conventional cancer‐therapeutic strategies, such as chemotherapy and surgery. The fast development of nanotechnology provides unprecedented superiorities for cancer therapeutics. Externally activatable therapeutic modalities mediated by nanomaterials, relying on highly effective energy transformation to release therapeutic elements/effects (cytotoxic reactive oxygen species, thermal effect, photoelectric effect, Compton effect, cavitation effect, mechanical effect or chemotherapeutic drug) for cancer therapies, categorized and termed as “energy‐converting nanomedicine,” have arouse considerable concern due to their noninvasiveness, desirable tissue‐penetration depth, and accurate modulation of therapeutic dose. This review summarizes the recent advances in the engineering of intelligent functional nanotherapeutics for energy‐converting nanomedicine, including photo‐based, radiation‐based, ultrasound‐based, magnetic field‐based, microwave‐based, electric field‐based, and radiofrequency‐based nanomedicines, which are enabled by external stimuli (light, radiation, ultrasound, magnetic field, microwave, electric field, and radiofrequency). Furthermore, biosafety issues of energy‐converting nanomedicine related to future clinical translation are also addressed. Finally, the potential challenges and prospects of energy‐converting nanomedicine for future clinical translation are discussed. 相似文献
4.
5.
Peng Zhang Zhiling Guo Zhiyong Zhang Hualing Fu Jason C. White Iseult Lynch 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(21)
Engineered nanomaterials (ENMs) have huge potential for improving use efficiency of agrochemicals, crop production, and soil health; however, the behavior and fate of ENMs and the potential for negative long‐term impacts to agroecosystems remain largely unknown. In particular, there is a lack of clear understanding of the transformation of ENMs in both soil and plant compartments. The transformation can be physical, chemical, and/or biological, and may occur in soil, at the plant interface, and/or inside the plant. Due to these highly dynamic processes, ENMs may acquire new properties distinct from their original profile; as such, the behavior, fate, and biological effects may also differ significantly. Several essential questions in terms of ENMs transformation are discussed, including the drivers and locations of ENM transformation in the soil–plant system and the effects of ENM transformation on analyte uptake, translocation, and toxicity. The main knowledge gaps in this area are highlighted and future research needs are outlined so as to ensure sustainable nanoenabled agricultural applications. 相似文献
6.
Qitao Hu;Huali Zuo;Jessica C. Hsu;Cheng Zeng;Zhou Tian;Zhouyi Sun;Weibo Cai;Zhe Tang;Weiyu Chen; 《Advanced materials (Deerfield Beach, Fla.)》2024,36(5):2308286
Cancer represents a serious disease with significant implications for public health, imposing substantial economic burden and negative societal consequences. Compared to conventional cancer treatments, such as surgery and chemotherapy, energy-based therapies (ET) based on athermal and thermal ablation provide distinct advantages, including minimally invasive procedures and rapid postoperative recovery. Nevertheless, due to the complex pathophysiology of many solid tumors, the therapeutic effectiveness of ET is often limited. Nanotechnology offers unique opportunities by enabling facile material designs, tunable physicochemical properties, and excellent biocompatibility, thereby further augmenting the outcomes of ET. Numerous nanomaterials have demonstrated the ability to overcome intrinsic therapeutic resistance associated with ET, leading to improved antitumor responses. This comprehensive review systematically summarizes the underlying mechanisms of ET-associated resistance (ETR) and highlights representative applications of nanoplatforms used to mitigate ETR. Overall, this review emphasizes the recent advances in the field and presents a detailed account of novel nanomaterial designs in combating ETR, along with efforts aimed at facilitating their clinical translation. 相似文献
7.
Sousa AA Morgan JT Brown PH Adams A Jayasekara MP Zhang G Ackerson CJ Kruhlak MJ Leapman RD 《Small (Weinheim an der Bergstrasse, Germany)》2012,8(14):2277-2286
Gold nanoparticles (AuNPs) with core sizes below 2 nm and compact ligand shells constitute versatile platforms for the development of novel reagents in nanomedicine. Due to their ultrasmall size, these AuNPs are especially attractive in applications requiring delivery to crowded intracellular spaces in the cytosol and nucleus. For eventual use in vivo, ultrasmall AuNPs should ideally be monodisperse, since small variations in size may affect how they interact with cells and how they behave in the body. Here we report the synthesis of ultrasmall, uniform 144-atom AuNPs protected by p-mercaptobenzoic acid followed by ligand exchange with glutathione (GSH). Quantitative scanning transmission electron microscopy (STEM) reveals that the resulting GSH-coated nanoparticles (Au(GSH)) have a uniform mass distribution with cores that contain 134 gold atoms on average. Particle size dispersity is analyzed by analytical ultracentrifugation, giving a narrow distribution of apparent hydrodynamic diameter of 4.0 ± 0.6 nm. To evaluate the nanoparticles' intracellular fate, the cell-penetrating peptide TAT is attached noncovalently to Au(GSH), which is confirmed by fluorescence quenching and isothermal titration calorimetry. HeLa cells are then incubated with both Au(GSH) and the Au(GSH)-TAT complex, and imaged without silver enhancement of the AuNPs in unstained thin sections by STEM. This imaging approach enables unbiased detection and quantification of individual ultrasmall nanoparticles and aggregates in the cytoplasm and nucleus of the cells. 相似文献
8.
Jingxing Si Shiqun Shao Youqing Shen Kai Wang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(37):5108-5119
Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor‐targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post‐surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR‐deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR‐deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR‐independent tumor‐targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy. 相似文献
9.
10.
11.
Goeun Choi;N. Sanoj Rejinold;Huiyan Piao;Young Bae Ryu;Hyung-Jun Kwon;In Chul Lee;Jeong In Seo;Hye Hyun Yoo;Geun-woo Jin;Jin-Ho Choy; 《Small (Weinheim an der Bergstrasse, Germany)》2024,20(39):2305148
The coronavirus disease 2019 (COVID-19) pandemic is a serious global threat with surging new variants of concern. Although global vaccinations have slowed the pandemic, their longevity is still unknown. Therefore, new orally administrable antiviral agents are highly demanded. Among various repurposed drugs, niclosamide (NIC) is the most potential one for various viral diseases such as COVID-19, SARS (severe acute respiratory syndrome), MERS (middle east respiratory syndrome), influenza, RSV (respiratory syncytial virus), etc. Since NIC cannot be effectively absorbed, a required plasma concentration for antiviral potency is hard to maintain, thereby restricting its entry into the infected cells. Such a 60-year-old bioavailability challenging issue has been overcome by engineering with MgO and hydroxypropyl methylcellulose (HPMC), forming hydrophilic NIC–MgO–HPMC, with improved intestinal permeability without altering NIC metabolism as confirmed by parallel artificial membrane permeability assay. The inhibitory effect on SARS-CoV-2 replication is confirmed in the Syrian hamster model to reduce lung injury. Clinical studies reveal that the bioavailability of NIC hybrid drug can go 4 times higher than the intact NIC. The phase II clinical trial shows a dose-dependent bioavailability of NIC from hybrid drug suggesting its potential applicability as a game changer in achieving the much-anticipated endemic phase. 相似文献
12.
13.
Denver P. Linklater Vladimir A. Baulin Xavier Le Guével Jean-Baptiste Fleury Eric Hanssen The Hong Phong Nguyen Saulius Juodkazis Gary Bryant Russell J. Crawford Paul Stoodley Elena P. Ivanova 《Advanced materials (Deerfield Beach, Fla.)》2020,32(52):2005679
It is commonly accepted that nanoparticles (NPs) can kill bacteria; however, the mechanism of antimicrobial action remains obscure for large NPs that cannot translocate the bacterial cell wall. It is demonstrated that the increase in membrane tension caused by the adsorption of NPs is responsible for mechanical deformation, leading to cell rupture and death. A biophysical model of the NP–membrane interactions is presented which suggests that adsorbed NPs cause membrane stretching and squeezing. This general phenomenon is demonstrated experimentally using both model membranes and Pseudomonas aeruginosa and Staphylococcus aureus, representing Gram-positive and Gram-negative bacteria. Hydrophilic and hydrophobic quasi-spherical and star-shaped gold (Au)NPs are synthesized to explore the antibacterial mechanism of non-translocating AuNPs. Direct observation of nanoparticle-induced membrane tension and squeezing is demonstrated using a custom-designed microfluidic device, which relieves contraction of the model membrane surface area and eventual lipid bilayer collapse. Quasi-spherical nanoparticles exhibit a greater bactericidal action due to a higher interactive affinity, resulting in greater membrane stretching and rupturing, corroborating the theoretical model. Electron microscopy techniques are used to characterize the NP–bacterial-membrane interactions. This combination of experimental and theoretical results confirm the proposed mechanism of membrane-tension-induced (mechanical) killing of bacterial cells by non-translocating NPs. 相似文献
14.
Sandeep Kumar Singh Venkatesh Teja Banala Girish K. Gupta Ashwni Verma Rahul Shukla Vivek K. Pawar 《Drug development and industrial pharmacy》2015,41(11):1759-1768
The aim of this study was to fabricate docetaxel loaded nanocapsules (DTX-NCs) with a high payload using Layer-by-Layer (LbL) technique by successive coating with alternate layers of oppositely charged polyelectrolytes. Developed nanocapsules (NCs) were characterized in terms of morphology, particle size distribution, zeta potential (ζ-potential), entrapment efficiency and in vitro release. The morphological characteristics of the NCs were assessed using transmission electron microscopy (TEM) that revealed coating of polyelectrolytes around the surface of particles. The developed NCs successfully attained a submicron particle size while the ζ-potential of optimized NCs alternated between (+) 34.64?±?1.5 mV to (?) 33.25?±?2.1 mV with each coating step. The non-hemolytic potential of the NCs indicated the suitability of the developed formulation for intravenous administration. A comparative study indicated that the cytotoxicity of positively charged NCs (F4) was significant higher (p?in vitro on MCF-7 cells. Furthermore, cell uptake studies evidenced a higher uptake of positive NCs (≥1.2 fold) in comparison to negative NCs. In conclusion, formulated NCs are an ideal vehicle for passive targeting of drugs to tumor cells that may result in improved efficacy and reduced toxicity of encapsulated drug moiety. 相似文献
15.
Claudia Contini Matthew Schneemilch Simon Gaisford 《Journal of Experimental Nanoscience》2018,13(1):62-81
Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes. 相似文献
16.
Rıfat Emrah Özel Ramiz S. J. Alkasir Kayla Ray Kenneth N. Wallace Silvana Andreescu 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(24):4250-4261
Nanoparticle (NP) exposure may induce oxidative stress through generation of reactive oxygen and nitrogen species, which can lead to cellular and tissue damage. The digestive system is one of the initial organs affected by NP exposure. Here, it is demonstrated that exposure to metal oxide NPs induces differential changes in zebrafish intestinal NO concentrations. Intestinal NO concentrations are quantified electrochemically with a carbon fiber microelectrode inserted in the intestine of live embryos. Specificity of the electrochemical signals is demonstrated by NO‐specific pharmacological manipulations and the results are correlated with the 4,5‐diaminofluorescein‐diacetate (DAF‐FM‐DA). NPs are demonstrated to either induce or reduce physiological NO levels depending on their redox reactivity, type and dose. NO level is altered following exposure of zebrafish embryos to CuO and CeO2 NPs at various stages and concentrations. CuO NPs increase NO concentration, suggesting an intestinal oxidative damage. In contrast, low CeO2 NP concentration exposure significantly reduces NO levels, suggesting NO scavenging activity. However, high concentration exposure results in increased NO. Alterations in NO concentration suggest changes in intestinal physiology and oxidative stress, which will ultimately correspond to NPs toxicity. This work also demonstrates the use of electrochemistry to monitor in vivo changes of NO within zebrafish organs. 相似文献
17.
Zhu Chen Jung Yeon Han Laura Shumate Renee Fedak Don L. DeVoe 《Advanced Materials Technologies》2019,4(6)
The use of additive manufacturing to fabricate microfluidic devices capable of high throughout synthesis of nanoscale liposomes with tunable dimensions is demonstrated. Employing a high‐resolution 3D printing process based on stereolithography and digital light projection, microchannel geometries and printing parameters are optimized to enable reliable patterning of channel features with critical dimensions of 200 µm, supporting the production of lipid vesicles below 100 nm in diameter by microfluidic flow focusing. The additive manufacturing approach enables the fabrication of flow focusing microchannels with high aspect ratios, together with seamless fabrication of high‐pressure fluidic ports for world‐to‐chip interfacing, supporting large volumetric flow rates and high‐throughput nanoparticle synthesis, with demonstrated production rates for optimized liposomes as high as 4 mg min−1 from a single device. 相似文献
18.
《Small Methods》2017,1(11)
Nanoparticles have received significant research interest for potential biomedical applications. Before nanomaterials are administered to patients, their biocompatibility should be thoroughly evaluated through in vitro experiments and other preclinical procedures. Many studies have sought to assess the toxicity of nanomaterials on synaptic transmission for neuroscience applications. However, it may be hard to perform such experiments because of the difficulty associated with delivering synthesized nanomaterials across cell membranes. Here, an in vitro method is demonstrated that mimics neuronal exocytosis, which features protein‐reconstituted liposomes for nanotoxicity testing; the effects of graphene oxide and pristine graphene on fusogenic activity and membrane integrity are examined. These results demonstrate the potential of this system as a novel in vitro platform for assessing the biocompatibility of nanomaterials, drug molecules, and other substances. 相似文献
19.
Liu X Sen S Liu J Kulaots I Geohegan D Kane A Puretzky AA Rouleau CM More KL Palmore GT Hurt RH 《Small (Weinheim an der Bergstrasse, Germany)》2011,7(19):2775-2785
This article reports a direct chemical pathway for antioxidant deactivation on the surfaces of carbon nanomaterials. In the absence of cells, carbon nanotubes are shown to deplete the key physiological antioxidant glutathione (GSH) in a reaction involving dissolved dioxygen that yields the oxidized dimer, GSSG, as the primary product. In both chemical and electrochemical experiments, oxygen is only consumed at a significant steady-state rate in the presence of both nanotubes and GSH. GSH deactivation occurs for single- and multi-walled nanotubes, graphene oxide, nanohorns, and carbon black at varying rates that are characteristic of the material. The GSH depletion rates can be partially unified by surface area normalization, are accelerated by nitrogen doping, and suppressed by defect annealing or addition of proteins or surfactants. It is proposed that dioxygen reacts with active sites on graphenic carbon surfaces to produce surface-bound oxygen intermediates that react heterogeneously with glutathione to restore the carbon surface and complete a catalytic cycle. The direct catalytic reaction between nanomaterial surfaces and antioxidants may contribute to oxidative stress pathways in nanotoxicity, and the dependence on surface area and structural defects suggest strategies for safe material design. 相似文献
20.
Saber M. Hussain Laura K. Braydich‐Stolle Amanda M. Schrand Richard C. Murdock Kyung O. Yu David M. Mattie John J. Schlager Mauricio Terrones 《Advanced materials (Deerfield Beach, Fla.)》2009,21(16):1549-1559
Recent developments in the field of nanotechnology involving the synthesis of novel nanomaterials (NM) have attracted the attention of numerous scientists owing to the possibility of degradative perturbations in human health. This Review evaluates previous investigations related to NM toxicity studies using biological models and describes the limitations that often prevent toxicologists from identifying whether NM pose a real hazard to human health. One major limitation to assess toxicity is the characterization of the NM prior to and after exposure to living cells or animals. The most relevant physicochemical characteristics of NM are: size, surface chemistry, crystallinity, morphology, solubility, aggregation tendency, homogeneity of dispersions, and turbidity. All of these properties need to be assessed in order to determine their contribution to toxicity. Due to the lack of appropriate methods to determine the physicochemical nature of nanoparticles in biological systems, the exact nature of NM toxicity is not fully described or understood at this time. This Review emphasizes the need for state‐of‐the‐art physicochemical characterization, the determination of appropriate exposure protocols and reliable methods for assessing NM internalization and their kinetics in living organisms. Once these issues are addressed, optimal experimental conditions could be established in order to identify if NM pose a threat to human health. Multidisciplinary research between materials scientists and life scientists should overcome these limitations in identifying the true hazards of NM. 相似文献