Merrittsaleh7603

Photothermal therapy (PTT) is a promising tumor treatment modality, but its efficacy is strictly hindered by abnormally upregulated heat shock proteins (HSPs) in tumor cells under heat stress. Herein, we developed a flower-like MnO2-coated polydopamine (PDA@MnO2) core-shell nanoplatform with the surface adsorption of HSP70-silencing DNAzyme (DZ) for enhanced PPT. The PDA core acted as a robust photothermal agent, and also as a reductant to allow the surface growth of MnO2via an in situ reduction of KMnO4. The MnO2 shell enabled a rapid and efficient adsorption of DZ, and more importantly, acted as a metal reservoir to release Mn2+ in response to intracellular stimuli for the in situ activation of DZ, which addressed the key limitation of DZ for biological applications, i.e., metal-dependent activity. As a result, HSP70 was remarkably suppressed for improved PTT efficacy upon laser irradiation, which was explicitly demonstrated both in vitro and in vivo. Upon intravenous injection, the nanosystem could effectively accumulate in the tumor, and impose potent PTT for complete tumor elimination via inducing tumor cell apoptosis, but without any noticeable toxicity. This work provides a promising nanosystem for enhanced PTT via silencing resistance-related genes, and offers ideas for the design of self-activated gene therapy platforms using DZ.Magnetic semiconductors with high critical temperature have long been the focus in materials science and are also known as one of the fundamental questions in two-dimensional (2D) materials. Based on density functional theory calculations, we predict a 2D spin-gapless ferromagnetic semiconductor of CrGa2Se4 monolayer, in which the type of spin-polarized current can be tuned by tailoring the Fermi energy. Moreover, the magnetic anisotropy energy calculations indicate that the CrGa2Se4 monolayer possesses spin anisotropy both in the basal plane and the vertical plane. This originates from the distortion-induced rearrangement of the 3d electrons in the CrSe6 octahedron and results in an inclined easy axis out of the film. The Curie temperature (Tc) of ferromagnetic phase transition for 2D CrGa2Se4 is more than 200 K. This 2D material shows promising transport properties for spintronics applications and is also important for fundamental research in 2D magnetism.DNA damage can take many forms such as double-strand breaks and/or the formation of abasic (apurinic/apyrimidinic; AP) sites. The presence of AP sites can be used to determine therapeutic efficacy of many drugs, such as doxorubicin. While there are different assays to search for DNA damage, they are fraught with limitations, such as the need for large amounts of DNA secured from millions of cells. This is challenging due to the growing importance of using liquid biopsies as a source of biomarkers for many in vitro diagnostic assays. To accommodate the mass limits imposed by the use of liquid biopsies, we report a single-molecule DNA damage assay that uses plastic nanofluidic chips to stretch DNA to near its full contour length when the channel dimensions (width and depth) are near the persistence length (∼50 nm) of double-stranded (ds) DNA. The nanofluidic chip consisted of input funnels for high loading efficiency of single DNA molecules, entropic traps to store the DNA and simultaneously load a series of nanochannels for high throughput processing, and an array of stretching nanochannels to read the AP sites. Single dsDNA molecules, which were labeled with an intercalating dye and a biotinylated aldehyde reactive probe (bARP), could be parked in the stretching nanochannels, where the AP sites were read directly using a dual-color fluorescence microscope equipped with an EMCCD camera. One color of the microscope was used to read the DNA length and the second color detected the AP sites. The nanofluidic chip was made from thermoplastics via nanoimprint lithography, which obviated the need for direct writing the devices in glass or quartz using focused ion beam milling. We show that we can read the frequency of AP sites in single dsDNA molecules with the frequency of AP sites determined by associating fluorescently-labeled streptavidin with bARP through a biotin/streptavidin complex.Transdermal microneedle (MN) drug delivery patches, comprising water-soluble polymers, have played an essential role in diverse biomedical applications, but with limited development towards fast deep release or sustained delivery applications. The effectiveness of such MN delivery patches strongly depends on the materials from which they are constructed. selleck compound Herein, we present a dual-action combinatorial programmable MN patch, comprising of fast and sustained-release MN zones, with tunable release kinetics towards delivering a wide range of therapeutics over different timeframes in single application. We demonstrate the fine tuning of MN materials; the patches can be tailored to deliver a first payload faster and deeper within minutes, while simultaneously delivering a second payload over long times ranging from weeks to months. The active and rapid burst release relies on embedding biodegradable Mg microparticle 'engines' in dissolvable MNs while the sustained release is attributed to biocompatible polymers that allow prolonged release in a controllable tunable manner. In addition, the patches are characterized and optimized for their design, materials and mechanical properties. These studies indicate that such programmable dual-action versatile MN platform is expected to improve therapeutic efficacy and patient compliance, achieving powerful benefits by single patch application at low manufacturing cost.Synthetic molecular recognition systems are increasingly being used to solve applied problems in the life sciences, and bio-targeted host-guest chemistry has rapidly arisen as a major field of fundamental research. This tutorial review presents a set of fundamental lessons on how host-guest molecular recognition can be programmed in water. The review uses informative examples of aqueous host-guest chemistry organized around generalizable themes and lessons, building towards lessons focused on molecular recognition in salty solutions and biological fluids. It includes selected examples of macrocyclic host systems that work well, as well as common pitfalls and how to avoid them. The review closes with a survey of the most important and inspirational recent advances, which involve host-guest chemistry in living cells and organisms.