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The spleen, body's largest secondary lymphoid organ, is also a vital hematopoietic and immunological organ. It is regarded as one of the most significant organs in humans. As more researchers recognize the functions of the spleen, clinical methods for treating splenic diseases and spleen-targeted drug delivery systems to improve the efficacy of spleen-related therapies have gradually developed. Many modification strategies (size, charge, ligand, protein corona) and hitchhiking strategies (erythrocytes, neutrophils) of nanoparticles (NPs) have shown a significant increase in spleen targeting efficiency. However, most of the targeted drug therapy strategies for the spleen are to enhance or inhibit the immune function of the spleen to achieve therapeutic effects, and there are few studies on spleen-related diseases. In this review, we not only provide a detailed summary of the design rules for spleen-targeted drug delivery systems in recent years, but also introduce common spleen diseases (splenic tumors, splenic injuries, and splenomegaly) with the hopes of generating more ideas for future spleen research.
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Sistemas de Liberação de Medicamentos , Baço , Esplenopatias , Humanos , Baço/metabolismo , Animais , Sistemas de Liberação de Medicamentos/métodos , Esplenopatias/tratamento farmacológico , Nanopartículas/administração & dosagemRESUMO
Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aß accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.
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Doença de Alzheimer , Vasos Linfáticos , Humanos , Camundongos , Animais , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Cilostazol , Donepezila , Acetilcolinesterase , Sistema Linfático/patologia , Encéfalo/patologia , DrenagemRESUMO
Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.
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Adiposidade , Obesidade , Feminino , Animais , Camundongos , Hiperplasia/metabolismo , Distribuição Tecidual , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Hipertrofia/patologia , Dieta Hiperlipídica/efeitos adversosRESUMO
Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.
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Arthritis is a syndrome characterized by inflammation in the joints. Triamcinolone acetonide (TA) was used as an anti-inflammatory agent in the treatment of this disease. However, there are limitations to its clinical application, including rapid clearance from the joint cavity, potential joint damage from multiple injections, and adverse joint events. To address these drawbacks, we developed a tunable in situ forming implant loaded with TA. This injectable polymer solution utilized poly (lactic-co-glycolic acid) (PLGA) as an extended-release material. When injected into the joints, the solution solidifies into implants through a solvent exchange in the aqueous environment. The implants demonstrated robust retention at the injection site and released TA over several weeks even months through diffusion and erosion. By adding different proportions of low water-miscible plasticizers, the release period of the drug could be precisely adjusted. The plasticizers-optimized implants exhibited a tough texture, enhancing the therapeutic efficiency and drug safety in vivo. In arthritic model studies, the tunable TA-loaded implants significantly reduced swelling, pain, and motor discoordination, and also showed suppression of arthritis progression to some extent. These findings suggested that TA-loaded ISFI holds promise for managing inflammatory disorders in individuals with arthritis.
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Artrite , Triancinolona Acetonida , Humanos , Solventes , Plastificantes , Anti-InflamatóriosRESUMO
Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.
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Glaucoma , Prostaglandinas F Sintéticas , Humanos , Latanoprosta/uso terapêutico , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio , alfa-Tocoferol , Pressão Intraocular , Glaucoma/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Prostaglandinas F Sintéticas/uso terapêuticoRESUMO
Nowadays, nanodrugs become a hotspot in the high-end medical field. They have the ability to deliver drugs to reach their destination more effectively due to their unique properties and flexible functionalization. However, the fate of nanodrugs in vivo is not the same as those presented in vitro, which indeed influenced their therapeutic efficacy in vivo. When entering the biological organism, nanodrugs will first come into contact with biological fluids and then be covered by some biomacromolecules, especially proteins. The proteins adsorbed on the surface of nanodrugs are known as protein corona (PC), which causes the loss of prospective organ-targeting abilities. Fortunately, the reasonable utilization of PC may determine the organ-targeting efficiency of systemically administered nanodrugs based on the diverse expression of receptors on cells in different organs. In addition, the nanodrugs for local administration targeting diverse lesion sites will also form unique PC, which plays an important role in the therapeutic effect of nanodrugs. This article introduced the formation of PC on the surface of nanodrugs and summarized the recent studies about the roles of diversified proteins adsorbed on nanodrugs and relevant protein for organ-targeting receptor through different administration pathways, which may deepen our understanding of the role that PC played on organ-targeting and improve the therapeutic efficacy of nanodrugs to promote their clinical translation.
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Nanopartículas , Coroa de Proteína , Nanopartículas/uso terapêutico , Estudos Prospectivos , Preparações Farmacêuticas , ProteínasRESUMO
Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases.
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In this paper, a hybrid wetting surface (HWS) with Au/Ag alloy nanocomposites was proposed for rapid, cost-effective, stable and sensitive SERS application. This surface was fabricated in a large area by facile electrospinning, plasma etching and photomask-assisted sputtering processes. The high-density 'hot spots' and rough surface from plasmonic alloy nanocomposites promoted the significant enhancement of the electromagnetic field. Meanwhile, the condensation effects induced by HWS further improved the density of target analytes at the SERS active area. Thus, the SERS signals increased ~4 orders of magnitude compared to the normal SERS substrate. In addition, the reproducibility, uniformity, as well as thermal performance of HWS were also examined by comparative experiments, indicating their high reliability, portability and practicability for on-site tests. The efficient results suggested that this smart surface had great potential to evolve as a platform for advanced sensor-based applications.
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Resonant integrated optical gyroscopes (RIOGs) can integrate discrete optical components as a promising candidate for high-performance micro-optical gyroscopes. However, the current RIOG still consists of discrete elements due to the difficulty and complexity of heterogeneous integration of resonator and modulators. This paper presents on-chip integration of optical functional components including modulator, resonator, beam splitter, and coupler for the organic-polymer-based RIOG. Simple integrated optical processes such as spin coating, lithography, and etching can realize RIOG chips with low cost, size, weight, and power (CSWaP) features. Thereinto, the electro-optic modulator (EOM) fabricated by self-synthesized electro-optic (EO) polymer (side chain bonded polyurethane imide) exhibits less than 2 V half-wave voltage, which is half of the lithium niobate (LiNbO3) modulator. With respect to the resonator, a quality factor of approximately million was achieved using low-loss fluorinated polymer. In addition, the angular velocity sensing of RIOG was also investigated. By demonstrating the monolithic integration of the resonator and modulators, such an all-polymer RIOG chip prototype builds the technical foundation for the precision fully integrated optical gyroscope.
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Organic-inorganic hybrid photodetectors have attracted increased interest due to their exceptional properties, such as flexibility, transparency, and low cost for many promising applications. Low-dimensional tungsten disulfide (WS2) nanostructures have outstanding electrical and optical properties, making them ideal candidates for ultrasensitive photodetector devices. In this paper, photodetectors were fabricated with hybrid thin films containing two different WS2 nanomaterials, one-dimensional (1D) WS2 nanotubes (WS2-NTs) and a zero-dimensional (0D) WS2 nanofullerene (WS2-FLs) hybrid with poly(N-vinyl carbazole) (PVK). The electrical responses of the devices under visible-light illuminations were studied. The photodetector devices with 0D WS2-FLs/PVK hybrid thin films have relatively higher sensitivity and stable voltage responses to visible light. Besides, the hybrid film shows a strong surface-enhanced Raman effect (SERS). These materials and new strategies enable the creation of a new class of processed photodetectors for practical applications.
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Excitons in two-dimensional (2D) materials have attracted the attention of the community to develop improved photoelectronic devices. Previous reports are based on direct excitation where the out-of-plane illumination projects a uniform single-mode light spot. However, because of the optical diffraction limit, the minimal spot size is a few micrometers, inhibiting the precise manipulation and control of excitons at the nanoscale level. Herein, we introduced the in-plane coherent surface plasmonic interference (SPI) field to excite and modulate excitons remotely. Compared to the out-of-plane light, a uniform in-plane SPI suggests a more compact spatial volume and an abundance of mode selections for a single or an array of device modulation. Our results not only build up a fundamental platform for operating and encoding the exciton states at the nanoscale level but also provide a new avenue toward all-optical integrated valleytronic chips for future quantum computation and information applications.
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Nanomaterials and nanostructures provide new opportunities to achieve high-performance optical and optoelectronic devices. Three-dimensional (3D) surfaces commonly exist in those devices (such as light-trapping structures or intrinsic grains), and here, we propose requests for nanoscale control over nanostructures on 3D substrates. In this paper, a simple self-assembly strategy of nanospheres for 3D substrates is demonstrated, featuring controllable density (from sparse to close-packed) and controllable layer (from a monolayer to multi-layers). Taking the assembly of wavelength-scale SiO2 nanospheres as an example, it has been found that textured 3D substrate promotes close-packed SiO2 spheres compared to the planar substrate. Distribution density and layers of SiO2 coating can be well controlled by tuning the assembly time and repeating the assembly process. With such a versatile strategy, the enhancement effects of SiO2 coating on textured silicon solar cells were systematically examined by varying assembly conditions. It was found that the close-packed SiO2 monolayer yielded a maximum relative efficiency enhancement of 9.35%. Combining simulation and macro/micro optical measurements, we attributed the enhancement to the nanosphere-induced concentration and anti-reflection of incident light. The proposed self-assembly strategy provides a facile and cost-effective approach for engineering nanomaterials at 3D interfaces.
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Organic-inorganic hybrid solar cells composed of p-type conducting polymer poly (3,4-ethylene-dioxythiophene): polystyrenesulfonate (PEDOT: PSS) and n-type silicon (Si) have gained considerable interest in recent years. From this viewpoint, we present an efficient hybrid solar cell based on PEDOT: PSS and the planar Si substrate (1 0 0) with the simplest and cost-effective experimental procedures. We study and optimize the thickness of the PEDOT: PSS film to improve the overall performance of the device. We also study the effect of ethylene glycol (EG) by employing a different wt % as a solvent in the PEDOT: PSS to improve the device's performance. Silver (Ag) was deposited by electron beam evaporation as the front and rear contacts for the solar cell device. The whole fabrication process was completed in less than three hours. A power conversion efficiency (PCE) of 5.1%, an open circuit voltage (Voc) of 598 mV, and a fill factor (FF) of 58% were achieved.
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We report a multi-step synthetic method to obtain ultrathin silver nanowires (Ag NWs) from an aqueous solution with a â¼17 nm diameter average, and where some of them decreased down to 9 nm. Carefully designed seed screening processes including LED irradiation at high temperature for a short time, and then continuous H2O2 etching, and relative growth mechanisms of high-yield five-twinned pentagonal seeds and ultrathin Ag NWs in aqueous environment are detailed. Then, a rapid and simple multiphase interfacial assembly method particularly suitable for the separation of ultrathin Ag NWs from various by-products was demonstrated with a clear mechanism explanation. Next, a unique optical interaction between light and individual AG NWs, as well as feature structures in the AG NWs film, was investigated by a micro-domain optical confocal microscope measurement in situ together with a theoretical explanation using modal transmission theory. That revealed that the haze problem of AG NWs films was not only arising from the interaction between light and individual or crossed Ag NWs but was also greatly dependent on a weak coupling effect of leaky modes supported by adjacent Ag NWs with large distances which had not been considered before. We then provided direct experimental evidence and concluded how to obtain haze-free films with 100% transparency in the whole visible range based on ultrathin Ag NWs. This breakthrough in diameter confinement and purification of Ag NWs is a highly expected step to overcome the well-focused light diffusion and absorption problems of Ag NWs-based devices applied in various fields such as flexible electronics, high-clarity displays, visible transparent heaters, photovoltaics and various optoelectronic technologies.