Nanoparticle-based drug delivery systems have been developed to improve the efficacy and reduce the systemic toxicity of a wide range of drugs. Although clinically approved nanoparticles have ...consistently shown value in reducing drug toxicity, their use has not always translated into improved clinical outcomes. This has led to the development of "multifunctional" nanoparticles, where additional capabilities like targeting and image contrast enhancement are added to the nanoparticles. However, additional functionality means additional synthetic steps and costs, more convoluted behavior and effects in vivo, and also greater regulatory hurdles. The trade-off between additional functionality and complexity is the subject of ongoing debate and the focus of this Review.
Amyloid precursor protein (APP) is processed sequentially by the β-site APP cleaving enzyme and γ-secretase to generate amyloid β (Aβ) peptides, one of the hallmarks of Alzheimer’s disease. The ...intracellular location of Aβ production—endosomes or the trans -Golgi network (TGN)—remains uncertain. We investigated the role of different postendocytic trafficking events in Aβ ₄₀ production using an RNAi approach. Depletion of Hrs and Tsg101, acting early in the multivesicular body pathway, retained APP in early endosomes and reduced Aβ ₄₀ production. Conversely, depletion of CHMP6 and VPS4, acting late in the pathway, rerouted endosomal APP to the TGN for enhanced APP processing. We found that VPS35 (retromer)-mediated APP recycling to the TGN was required for efficient Aβ ₄₀ production. An interruption of the bidirectional trafficking of APP between the TGN and endosomes, particularly retromer-mediated retrieval of APP from early endosomes to the TGN, resulted in the accumulation of endocytosed APP in early endosomes with reduced APP processing. These data suggest that Aβ ₄₀ is generated predominantly in the TGN, relying on an endocytosed pool of APP recycled from early endosomes to the TGN.
The ability of chelated Gd to serve as an effective magnetic resonance (MR) contrast agent largely depends on fast exchange rates between the Gd-bound water molecules and the surrounding bulk water. ...Because water diffuses slowly across lipid bilayers, liposomes with encapsulated chelated Gd have not been widely adopted as MR contrast agents. To overcome this limitation, we have synthesized chemically stabilized, porous polymersomes with encapsulated gadolinium (Gd) chelates. The polymerosmes, 125 nm in diameter, were produced from the aqueous assembly of diblock copolymers, PEO(1300)-b-PBD(2500) (PBdEO), and phospholipids, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The PBdEO was cross-linked using a chemical initiator and the POPC was extracted with surfactant, generating a highly porous outer membrane. The encapsulated Gd chelates were attached to dendrimers to prevent their leakage through the pores. It was estimated that, on average, nearly 44 000 Gd were encapsulated within each polymersome. As a result of the slower rotational correlation time of Gd-labeled dendrimers and the porous outer membrane, the paramagnetic porous polymersomes exhibited an R1 relaxivity of 7.2 mM−1 s1− per Gd and 315 637 mM−1 s−1 per vesicle. This corresponds to a relaxivity that is amplified by a factor of ∼105 compared with Gd−DTPA.
Metallic 1T-phase transition metal dichalcogenides (TMDs) are of considerable interest in enhancing catalytic applications due to their abundant active sites and good conductivity. However, the ...unstable nature of 1T-phase TMDs greatly impedes their practical applications. Herein, we developed a new approach for the synthesis of highly stable 1T-phase Au/Pd-MoS2 nanosheets (NSs) through a metal assembly induced ultrastable phase transition for achieving a very high electrocatalytic activity in the hydrogen evolution reaction. The phase transition was evoked by a novel mechanism of lattice-mismatch-induced strain based on density functional theory (DFT) calculations. Raman spectroscopy and transmission electron microscopy (TEM) were used to confirm the phase transition on experimental grounds. A novel heterostructured 1T MoS2–Au/Pd catalyst was designed and synthesized using this mechanism, and the catalyst exhibited a 0 mV onset potential in the hydrogen evolution reaction under light illumination. Therefore, this method can potentially be used to fabricate 1T-phase TMDs with remarkably enhanced activities for different applications.
Osteoarthritis (OA) is a widespread joint disease for which there are no disease-modifying treatments. Previously, we found that mice with cartilage-specific epidermal growth factor receptor (EGFR) ...deficiency developed accelerated knee OA. To test whether the EGFR pathway can be targeted as a potential OA therapy, we constructed two cartilage-specific EGFR overactivation models in mice by overexpressing heparin binding EGF-like growth factor (HBEGF), an EGFR ligand. Compared to wild type, Col2-Cre HBEGF-overexpressing mice had persistently enlarged articular cartilage from adolescence, due to an expanded pool of chondroprogenitors with elevated proliferation ability, survival rate, and lubricant production. Adult Col2-Cre HBEGF-overexpressing mice and Aggrecan-CreER HBEGF-overexpressing mice were resistant to cartilage degeneration and other signs of OA after surgical destabilization of the medial meniscus (DMM). Treating mice with gefitinib, an EGFR inhibitor, abolished the protective action against OA in HBEGF-overexpressing mice. Polymeric micellar nanoparticles (NPs) conjugated with transforming growth factor-α (TGFα), a potent EGFR ligand, were stable and nontoxic and had long joint retention, high cartilage uptake, and penetration capabilities. Intra-articular delivery of TGFα-NPs effectively attenuated surgery-induced OA cartilage degeneration, subchondral bone plate sclerosis, and joint pain. Genetic or pharmacologic activation of EGFR revealed no obvious side effects in knee joints and major vital organs in mice. Together, our studies demonstrate the feasibility of using nanotechnology to target EGFR signaling for OA treatment.
Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater ...X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image contrast, and serve as a radiosensitizer, gold-loaded polymeric micelles (GPMs) were prepared. Specifically, 1.9 nm AuNPs were encapsulated within the hydrophobic core of micelles formed with the amphiphilic diblock copolymer poly(ethylene glycol)-b-poly(ε-capralactone). GPMs were produced with low polydispersity and mean hydrodynamic diameters ranging from 25 to 150 nm. Following intravenous injection, GPMs provided blood pool contrast for up to 24 h and improved the delineation of tumor margins via CT. Thus, GPM-enhanced CT imaging was used to guide radiation therapy delivered via a small animal radiation research platform. In combination with the radiosensitizing capabilities of gold, tumor-bearing mice exhibited a 1.7-fold improvement in the median survival time, compared with mice receiving radiation alone. It is envisioned that translation of these capabilities to human cancer patients could guide and enhance the efficacy of radiation therapy.
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•Superhydrophobic meshes covered with nanostructured FAS grafted electroless Ni-P plating coating were prepared.•The meshes can rapidly and continuously separate oil-water mixture ...without any extra driving force and chemical agent.•The superhydrophobic mesh is steady and reliable for the long-term separation of the water-oil mixture.•A separation model of water-oil mixture through the superhydrophobic or hydrophobic meshes was proposed.
The development of the super-hydrophobic coating/film mesh for directly separating oil from water is greatly desired due to the high separation efficiency and the steady recyclability. Here we describe a facile and inexpensive method for fabricating the super-hydrophobic/super-oleophilic stainless steel meshes with the FAS modified electroless Ni-P composite coatings. The Ni-P particles on the mesh are spherical with a uniform size diameter and relatively concatenate each other to form a nanoscale rough surface. The static contact angles of the as-prepared meshes fall in between 124.4 ± 1.5° and 167.9 ± 2.1°. These meshes exhibit non-sticking of water, anti-fouling, and excellent penetrating through the oil properties. The prepared meshes can rapidly and continuously separate water-oil mixture without resorting to any extra driving force and the chemical agent. The best separation efficiency is 96.8%. The super-hydrophobic mesh is steady and reliable for a long-term separation of the water-oil mixtures. Finally, a separation mechanism of the super-hydrophobic meshes for the water-oil mixtures is proposed. We anticipate that the prepared meshes could provide a candidate application to effective waste oil cleanup and other rapid water-oil separation processes.
Photodynamic therapy (PDT) has attracted widespread attention in recent years as a noninvasive and highly selective approach for cancer treatment. We have previously reported a significant increase ...in the 90-day complete response rate when tumor-bearing mice are treated with the epidermal growth factor receptor (EGFR) inhibitor erlotinib prior to PDT with the photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA) compared to treatment with PDT alone. To further explore this strategy for anticancer therapy and clinical practice, we tested whether pretreatment with erlotinib also exhibited a synergistic therapeutic effect with a nanocarrier containing the clinically relevant photosensitizer protoporphyrin IX (PpIX). The PpIX was encapsulated within biodegradable polymeric micelles formed from the amphiphilic block copolymer poly(ethylene glycol)–polycaprolactone (PEG–PCL). The obtained micelles were characterized systematically in vitro. Further, an in vitro cytotoxicity study showed that PDT with PpIX loaded micelles did exhibit a synergistic effect when combined with erlotinib pretreatment. Considering the distinct advantages of polymeric nanocarriers in vivo, this study offers a promising new approach for the improved treatment of localized tumors. The strategy developed here has the potential to be extended to other photosensitizers currently used in the clinic for photodynamic therapy.
Highlights
Single-atom Co–MoS
2
(SA Co–MoS
2
) is prepared successfully to serve as a proof-of-concept nanozyme model, which exhibits peroxidase-like performance comparable to that of natural ...enzymes.
The different mechanisms between the single-atom metal center and the support are investigated experimentally and theoretically.
The single-atom nanozyme is a new concept and has tremendous prospects to become a next-generation nanozyme. However, few studies have been carried out to elucidate the intrinsic mechanisms for both the single atoms and the supports in single-atom nanozymes. Herein, the heterogeneous single-atom Co–MoS
2
(SA Co–MoS
2
) is demonstrated to have excellent potential as a high-performance peroxidase mimic. Because of the well-defined structure of SA Co–MoS
2
, its peroxidase-like mechanism is extensively interpreted through experimental and theoretical studies. Due to the different adsorption energies of substrates on different parts of SA Co–MoS
2
in the peroxidase-like reaction, SA Co favors electron transfer mechanisms, while MoS
2
relies on Fenton-like reactions. The different catalytic pathways provide an intrinsic understanding of the remarkable performance of SA Co–MoS
2
. The present study not only develops a new kind of single-atom catalyst (SAC) as an elegant platform for understanding the enzyme-like activities of heterogeneous nanomaterials but also facilitates the novel application of SACs in biocatalysis.
•A novel ultrasonic-ozone-coupled dye effluent treatment system was developed.•A detailed analysis of the flow state of the experimental device was conducted using CFD simulation method.•The addition ...of ultrasound increased the RhB reaction rate constant from 0.0134 min-1 to 0.0372 min-1.•Ultrasound can effectively control membrane fouling.
In this study, ozone catalysts (hydrogenation-modified red mud, HM-RM) successfully prepared by hydrogenation-modification of industrial hazardous solid waste red mud (RM) as a raw material in accordance with the viewpoint of treating waste with waste and using waste. Meanwhile, as for the common phenomenon of membrane fouling, uneven distribution of multiphase solid catalysts and ozone in liquids, the addition of ultrasound can not only disperse materials, but also play a role in online cleaning of ceramic membranes and catalysts. The optimum treatment conditions for Rhodamine B (RhB) solution with volume of 2 L and concentration of 40 mg/L were catalyst concentration of 0.4 mg/L, reaction temperature of 45 °C, ultrasonic time of 1 h, ultrasonic intensity of 600 W, removal rate of RhB was up to 90 %. In addition, the computational fluid dynamics (CFD) simulation method was used to investigate the fluid flow between the two gas-liquid phases and the effect of the negative pressure of the membrane pump on the fluid by the analysis of flow, pressure and ozone flux of the ceramic membrane(CM) reaction apparatus. The CFD simulation results showed that at the inlet gas-liquid flow rate of 3 m/s and the negative pressure of 20,000 Pa, the maximum flow rates of CM-1 were 3 m/s, 0.752 m/s for CM-2, and 0.228 m/s for CM-3, respectively. Vortices, which are beneficial to solid-liquid mixing and gas-liquid mass transfer, formed between the suction port CM-1 of CM-1 and the inlets of CM-2 and CM-3. This discovery is consistent with relevant experimental research results. Significantly higher concentrations of both •OH and dissolved ozone were observed in the US/HM-RM/O3 system compared to other systems, indicating the significant improvement in ozone utilization rate through the application of ultrasound. The superiority of the US/HM-RM/O3 device was demonstrated. The real dye effluent was tested under optimum operating conditions and the results showed that COD and TOC were reduced by 81.34 % and 60.23 % respectively after 180 min of treatment. The above research can provide technical support for the treatment of dye wastewater using Ultrasound-enhanced ozone oxidation ceramic membranes.
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