Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the ...identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
Synthesis, characterization, and applications of colloidal nanoparticles have been a prominent topic of current research interests within the last two decades. Available reports in the literature ...that describe the synthesis of colloidal nanoparticles are abundant with various degrees of reproducibility and simplicity. Moreover, different methods for the characterization of colloidal nanoparticle’s basic properties are employed, resulting in conflicting results in many cases. Herein, we describe “in detail” selected standard protocols for the synthesis, purification, and characterization of various types of colloidal inorganic nanoparticles including gold nanoparticles, silver nanoparticles, iron oxide nanoparticles, and quantum dots. This report consists of five main parts: The first and the second parts are dedicated to describing the synthesis of various types of hydrophobic and hydrophilic nanoparticles in organic solvents and in aqueous solutions, respectively. The third part describes surface modification of nanoparticles with a focus on ligand exchange reactions, to allow phase transfer of nanoparticles from aqueous to organic solvents and vice versa. The fourth and the fifth parts describe various general purification and characterization techniques used to purify and characterize nanoparticles, respectively. Collectively, this contribution does not aim to cover all available protocols in the literature to prepare inorganic nanoparticles but rather provides detailed synthetic procedures for important inorganic nanocrystals with a full description of their purification and characterization process.
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A plasmonic core–shell gold nanostar/zeolitic‐imidazolate‐framework‐8 (ZIF‐8) nanocomposite was developed for the thermoplasmonic‐driven release of encapsulated active molecules inside living cells. ...The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF‐8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule‐release mechanism relies on the use of near‐IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near‐IR‐triggered cargo release inside cells, thereby leading to DNA staining.
Triggered release: A thermoresponsive carrier comprising gold nanostars coated with ZIF‐8 stabilized with an amphiphilic polymer was developed for the light‐triggered release of encapsulated cargo inside cells. This nanocomposite, which is stable in aqueous solution (even when stored in cells), combines thermoplasmonic and high drug‐loading capabilities.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A homologous nanoparticle library was synthesized in which gold nanoparticles were coated with polyethylene glycol, whereby the diameter of the gold cores, as well as the thickness of the shell of ...polyethylene glycol, was varied. Basic physicochemical parameters of this two‐dimensional nanoparticle library, such as size, ζ‐potential, hydrophilicity, elasticity, and catalytic activity ,were determined. Cell uptake of selected nanoparticles with equal size yet varying thickness of the polymer shell and their effect on basic structural and functional cell parameters was determined. Data indicates that thinner, more hydrophilic coatings, combined with the partial functionalization with quaternary ammonium cations, result in a more efficient uptake, which relates to significant effects on structural and functional cell parameters.
A homologous library of gold nanoparticles coated with polyethylene glycol was synthesized, whereby the diameter of the gold cores, as well as the thickness of the shell of polyethylene glycol, was varied. Basic physicochemical parameters of this two‐dimensional nanoparticle library were determined. Cell uptake of selected nanoparticles and their effect on basic structural and functional cell parameters were determined.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides ...tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device.
Too hot to handle: The surroundings of magnetic nanoparticles can be heated by applying a magnetic field. Polymer‐coated magnetic nanoparticles were functionalized with single‐stranded DNA molecules ...and further hybridized with DNA modified with different fluorophores. By correlating the denaturation profiles of the DNA with the local temperature, temperature gradients for the vicinity of the excited nanoparticles were determined.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The field of nanotechnology applied to medicine (nanomedicine) is developing at a fast pace and is expected to provide solutions for early diagnosis, targeted therapy, and personalized medicine. ...However, designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, control over the interaction of a nanomaterial with biological entities such as proteins and cell membranes, low toxicity, and optimal bioperformance are critical for the success of the designed nanomaterial. In this Feature Article we provide a concise overview of some of the most recent advances concerning the derivatization of gold and iron oxide nanoparticles for bioapplications. The most important aspects relating to the functionalization of gold and iron oxide nanoparticles with carbohydrates, peptides, nucleic acids, and antibodies are covered, highlighting the recent contributions from our research group. We suggest tips for the appropriate (bio)functionalization of these inorganic nanoparticles in order to preserve the biological activity of the attached biomolecules and ensure their subsequent stability in physiological media.
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We present an all-optical modulator based on manganese ferrite nanoparticles (MnFe2O4 NPs), which provides an enhanced attenuation of broad-band terahertz waves. A wide-band modulation of THz ...transmission was observed in a frequency range from 0.15 to 1.2 THz. The experimental results were assessed by simulations in the context of a band structure model of semiconductors. Our work demonstrated that coatings of MnFe2O4 NPs can be efficiently used to improve the performance of THz modulators based on optical modulation. This paper describes a new route to increase the surface photoconductivity of semiconductors by coating of MnFe2O4 NPs. This work demonstrates that the THz modulator based on MnFe2O4 NPs can significantly boost the overall performance of THz communication systems, and MnFe2O4 NPs may offer some useful solutions for future THz devices.
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Metal-organic frameworks (MOFs) are extremely versatile materials, which serve to create platforms with exceptional porosity and specific reactivities. The production of MOFs at the nanoscale (NMOFs) ...offers the possibility of creating innovative materials for bioapplications as long as they maintain the properties of their larger counterparts. Due to their inherent chemical versatility, synthetic methods to produce them at the nanoscale can be combined with inorganic nanoparticles (NPs) to create nanocomposites (NCs) with one-of-a-kind features. These systems can be remotely controlled and can catalyze abiotic reactions in living cells, which have the potential to stimulate further research on these nanocomposites as tools for advanced therapies.
Metal-organic frameworks (MOFs) are extremely versatile materials, which serve to create platforms with exceptional porosity and specific reactivities.
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