Although clozapine, olanzapine, and other atypical antipsychotic drugs (APDs) have fewer extrapyramidal side effects, they have serious metabolic side effects such as substantial weight gain, ...intra-abdominal obesity, and type 2 diabetes mellitus. Given that most patients with mental disorders face chronic, even life-long, treatment with APDs, the risks of weight gain/obesity and other metabolic symptoms are major considerations for APD maintenance treatment. This review focuses on the effects of APDs on weight gain, appetite, insulin resistance, and glucose dysregulation, and the relevant underlying mechanisms that may be help to prevent and treat metabolic side effects caused by APD therapy.
In recent years, polymeric nanoparticles have appeared as a most viable and versatile delivery system for targeted cancer therapy. Various in vivo studies have demonstrated that virus-sized stealth ...particles are able to circulate for a prolonged time and preferentially accumulate in the tumor site via the enhanced permeability and retention (EPR) effect (so-called “passive tumor-targeting”). The surface decoration of stealth nanoparticles by a specific tumor-homing ligand, such as antibody, antibody fragment, peptide, aptamer, polysaccharide, saccharide, folic acid, and so on, might further lead to increased retention and accumulation of nanoparticles in the tumor vasculature as well as selective and efficient internalization by target tumor cells (termed as “active tumor-targeting”). Notably, these active targeting nanoparticulate drug formulations have shown improved, though to varying degrees, therapeutic performances in different tumor models as compared to their passive targeting counterparts. In addition to type of ligands, several other factors such as in vivo stability of nanoparticles, particle shape and size, and ligand density also play an important role in targeted cancer chemotherapy. In this review, concept and recent development of polymeric nanoparticles conjugated with specific targeting ligands, ranging from proteins (e.g., antibodies, antibody fragments, growth factors, and transferrin), peptides (e.g., cyclic RGD, octreotide, AP peptide, and tLyp-1 peptide), aptamers (e.g., A10 and AS1411), polysaccharides (e.g., hyaluronic acid), to small biomolecules (e.g., folic acid, galactose, bisphosphonates, and biotin), for active tumor-targeting drug delivery in vitro and in vivo are highlighted and discussed. With promise to maximize therapeutic efficacy while minimizing systemic side effects, ligand-mediated active tumor-targeting treatment modality has become an emerging and indispensable platform for safe and efficient cancer therapy.
•A modified coaxial electrospinning for creating hypromellose-based composite fibers.•Quantitative analyses of Taylor cone and straight fluid jet during electrospinning.•Amorphous hydrophilic ...nanocomposites consisting of multiple components.•Improved performances about the fast dissolution of poorly water-soluble drug.
Hypromellose (HPMC)-based hydrophilic composites (HCs) used for rapid dissolution of ferulic acid (FA) were investigated. Electrospun and casting HCs were prepared from a solution containing HPMC, FA, and polyethylene glycol. Ethanol was used as sheath fluid during coaxial processes, and the effects of its flow rates on the Taylor cone and straight fluid jet were investigated. The morphology, component state, hydrophilicity, and drug dissolution rate of the HCs were characterized. Results demonstrated that all HCs were amorphous materials, and their components were compatible. However, the dissolution rate of electrospun HCs was 10 times faster than that of casting HCs. The smaller the diameters of electrospun HCs were, the better their performances were. The mechanism of electrospun HCs was suggested. By utilizing modified coaxial electrospinning and combinations of drug carriers, new types of HPMC-based HCs can provide an alternative approach for the effective delivery of poorly water-soluble drugs.
•Gives an overview on biosignals existing in the tumor and tumor cells.•Illustrates the potential impacts and uses of biosignals on anticancer drug delivery.•Highlights the design rationale and ...recent exciting development of bioresponsive polymeric nanotherapeutics for targeted cancer chemotherapy.•Presents personal perspectives on the challenges and future development of translational nanomedicine based on bioresponsive polymeric nanotherapeutics.
In recent years, bioresponsive polymeric nanotherapeutics that facilitate tumor cell uptake and trigger drug release at the target site have emerged as a fascinating platform for safe and efficient cancer therapy. The naturally occurring environments such as tumor acidity, tumor extracellular enzymes like matrix metalloproteases (MMP), endo/lysosomal pH, elevated glutathione levels in the cytoplasm and cell nucleus, lysosomal enzymes, as well as reactive oxygen species (ROS) in the mitochondria have been exploited as potential internal stimuli to achieve active drug and protein release in the tumor tissue or cancer cells. These bioresponsive nanosystems present several unique features such as no need of an external device, precision control over site of response (from tumor tissue down to cellular organelle level) following accumulation in the tumor via either passive or active targeting, and spontaneous activation in the tumor site or inside the tumor cells. In this review, we highlight the design rationale and recent exciting development of bioresponsive polymeric nanotherapeutics for enhanced cancer treatments with low side effects.
Abstract
Color-saturated green-emitting molecules with high Commission Internationale de L’Eclairage (CIE) y values have great potential applications for displays and imaging. Here, we linked the ...outer phenyl groups in multiple-resonance (MR)-type blue-emitting B (boron)-N (nitrogen) molecules through bonding and spiro-carbon bridges, resulting in rigid green emitters with thermally activated delayed fluorescence. The MR effect and multiple interlocking strategy greatly suppressed the high-frequency vibrations in the molecules, which emit green light with a full-width at half-maximum of 14 nm and a CIE y value of 0.77 in cyclohexane. These were the purest green molecules with quantum efficiency and color purity that were comparable with current best quantum dots. Doping these emitters into a traditional green-emitting phosphorescence organic light-emitting diode (OLED) endowed the device with a Broadcast Service Television 2020 color-gamut, 50% improved external quantum efficiency, and an extremely high luminescence of 5.1 × 10
5
cd/m
2
, making it the greenest and brightest OLED ever reported.
The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that ...(i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeutics (e.g. peptide and protein drugs, and siRNA) exert therapeutical effects only inside cells like the cytosol and cell nucleus, and (ii) several intracellular compartments such as cytosol, mitochondria, and cell nucleus contain a high concentration of glutathione (GSH) tripeptides (about 2–10
mM), which is 100 to 1000 times higher than that in the extracellular fluids and circulation (about 2–20
μM). Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of nano-carriers inside cells to accomplish efficient intracellular drug release. In this paper, we will review recent results on GSH-responsive nano-vehicles in particular micelles, nanoparticles, capsules, polymersomes, nanogels, dendritic and macromolecular drug conjugates, and nano-sized nucleic acid complexes for controlled delivery of anti-cancer drugs (e.g. doxorubicin and paclitaxel), photosensitizers, anti-oxidants, peptides, protein drugs, and nucleic acids (e.g. DNA, siRNA, and antisense oligodeoxynucleotide). The unique disulfide chemistry has enabled novel and versatile designs of multifunctional delivery systems addressing both intracellular and extracellular barriers. We are convinced that GSH-responsive nano-carrier systems have enormous potential in targeted cancer therapy.
Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of reduction-sensitive nano-carriers inside cells particularly in the endo/lysosome, cytosol, and cell nucleus to achieve efficient intracellular drug and gene release.
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The existence of drug resistance poses a major obstacle for the treatment of various malignant human cancers. Here, we report on reduction-sensitive reversibly crosslinked hyaluronic acid (HA) ...nanoparticles based on HA-Lys-LA conjugates (Lys: l-lysine methyl ester, LA: lipoic acid) for active targeting delivery of doxorubicin (DOX) to CD44+ breast cancers in vitro and in vivo, effectively overcoming drug resistance (ADR). HA-Lys-LA with degrees of substitution of 5, 10 and 28% formed robust nano-sized nanoparticles (152–219nm) following auto-crosslinking. DOX-loaded crosslinked nanoparticles revealed inhibited DOX release under physiological conditions while fast drug release in the presence of 10mM glutathione (GSH). Notably, MTT assays showed that DOX-loaded crosslinked HA-Lys-LA10 nanoparticles possessed an apparent targetability and a superior antitumor activity toward CD44 receptor overexpressing DOX-resistant MCF-7 human breast cancer cells (MCF-7/ADR). The in vivo pharmacokinetics and biodistribution studies in MCF-7/ADR tumor xenografts in nude mice showed that DOX-loaded crosslinked HA-Lys-LA10 nanoparticles had a prolonged circulation time and a remarkably high accumulation in the tumor (12.71%ID/g). Notably, DOX-loaded crosslinked HA-Lys-LA10 nanoparticles exhibited effective inhibition of tumor growth while continuous tumor growth was observed for mice treated with free drug. The Kaplan–Meier survival curves showed that in contrast to control groups, all mice treated with DOX-loaded crosslinked HA-Lys-LA10 nanoparticles survived over an experimental period of 44days. Importantly, DOX-loaded crosslinked HA nanoparticles caused low side effects. The reversibly crosslinked hyaluronic acid nanoparticles with excellent biocompatibility, CD44-targetability, and effective reversal of drug resistance have a great potential in cancer therapy.
Robust, biocompatible and multifunctional hyaluronic acid nanoparticles mediate specific and efficient delivery and release of doxorubicin to CD44-positive drug-resistant human breast cancers in vitro and in vivo, inducing effective reversal of drug resistance, high therapeutic efficacy and low side effects. Display omitted
Recently, we have read with great interest the original article used different spatial configuration models of colorectal cancer (CRC) for validating the anti-tumor efficacy with Diiminoquinone. We ...feel obliged to provide new insight into the drug screening models by integrating and analyzing the original method and result. These comments may provide comprehensive insights into three-dimensional drug screening models and the difference between pathologic subtypes in CRC.
Blue phosphorus is a new graphene-like material which has already been proven thermostable in theory, and the synthesis of it on experiment can also be expected. Here, we have investigated the ...electronic structures and carrier mobilities of armchair and zigzag monolayer blue phosphorus nanoribbons (PNRs) and nanotubes (PNTs) using density functional theory combined with Boltzmann transport method with relaxation time approximation. It is found that both PNRs and PNTs are indirect-gap semiconductors with a considerable energy gap. The numerical calculation results indicate that the armchair PNTs, zigzag PNTs, and armchair PNRs have the characteristics of p-type semiconductors in electrical conduction, because the hole mobility is over 1 order larger than the electron mobility. However, the electron mobility is greater than the hole mobility in zigzag PNRs. Owing to the existing p x orbitals (in-plane and along ribbon direction), which are very sensitive to the atomic structure strain, the band edges will be significantly changed under strain which results in a linear decrease of the gap of PNRs and PNTs with deformation aggravation. The charge mobilities can also be effectively regulated by the strain.
Abstract
Planar digital image sensors facilitate broad applications in a wide range of areas
1–5
, and the number of pixels has scaled up rapidly in recent years
2,6
. However, the practical ...performance of imaging systems is fundamentally limited by spatially nonuniform optical aberrations originating from imperfect lenses or environmental disturbances
7,8
. Here we propose an integrated scanning light-field imaging sensor, termed a meta-imaging sensor, to achieve high-speed aberration-corrected three-dimensional photography for universal applications without additional hardware modifications. Instead of directly detecting a two-dimensional intensity projection, the meta-imaging sensor captures extra-fine four-dimensional light-field distributions through a vibrating coded microlens array, enabling flexible and precise synthesis of complex-field-modulated images in post-processing. Using the sensor, we achieve high-performance photography up to a gigapixel with a single spherical lens without a data prior, leading to orders-of-magnitude reductions in system capacity and costs for optical imaging. Even in the presence of dynamic atmosphere turbulence, the meta-imaging sensor enables multisite aberration correction across 1,000 arcseconds on an 80-centimetre ground-based telescope without reducing the acquisition speed, paving the way for high-resolution synoptic sky surveys. Moreover, high-density accurate depth maps can be retrieved simultaneously, facilitating diverse applications from autonomous driving to industrial inspections.
