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Tin (Sn)-based perovskites are being investigated in many optoelectronic applications given their similar valence electron configuration to that of lead-based perovskites and the potential environmental hazards of lead-based perovskites. However, the formation of high-quality Sn-based perovskite films faces several challenges, mainly due to the easy oxidation of Sn2+ to Sn4+ and the fast crystallization rate. Here, to develop an environmentally friendly process for Sn-based perovskite fabrication, a series of natural antioxidants are studied as additives and ascorbic acid (VitC) is found to have a superior ability to inhibit the oxidation problem. A common cyclic molecule, 18-Crown-6, is further added as a second additive, which synergizes with VitC to significantly reduce the nonradiative recombination pathways in the PEA2SnI4 film. This synergistic effect greatly improves the performance of 2D red Sn-based PeLED, with a maximum external quantum efficiency of 1.87% (≈9 times that of the pristine device), a purer color, and better bias stability. This work demonstrates the potential of the dual-additive approach in enhancing the performance of 2D Sn-based PeLEDs, while the use of these environmentally friendly additives contributes to their future sustainability.
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The development of single-component organic solar cells (SCOSCs) using only one photoactive component with a chemically bonded D/A structure has attracted increasing research attention in recent years. At represent, most relevant studies focus on comparing the performance difference between a donor-acceptor (D-A) conjugated block copolymer (CBC) and the commensurate blending systems based on the same donor and acceptor segments, and still there are no reports on the impact of the segment ratio for a certain D-A CBC on the resultant photovoltaic performance. In this study, we synthesized a D-A all-conjugated polymers based on an n-type PNDI2T block and a p-type PBDB-T donor block but with three different segment ratios (P1-P3) and demonstrate the significance of the D/A segment ratio on photovoltaic performance. Our results reveal that the n-type PNDI2T block plays a more critical role in the inter/intra-chain charge transfer. P1 with a higher content of PNDI2T delivers superior exciton dissociation and charge transfer behavior than P2 and P3, benefitting from its more balanced hole/electron mobility. In addition, a higher packing regularity associated with a more dominant face-on orientation is also observed for P1. As a result, SCOSC based on P1 exhibits the highest PCE among the synthesized CBCs. It also possesses a minimal energy loss due to the better suppressed non-radiative recombination loss. This work provides the first discussion of the impact of the segment ratio for a D-A all-conjugated block copolymer and signifies the critical role of the n-type segment in designing high-performance single-component CBCs.
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We develop a temperature-programmed pretreatment strategy for converting aliphatic-rich petroleum pitch into a mesophase framework, which can then be activated using KOH to produce high-performance carbons for electric double-layer capacitors (EDLCs). In the pretreatment of pitch at an optimal temperature, both the temperature ramp and holding time influence the mesophase structure, which governs the pore structure and crystallinity of the resulting activated carbon. High carbon microporosity is beneficial to capacitance maximization but detrimental to ion transport. To resolve this problem, we develop a multistep ramp incorporating aliphatic species into the aromatic framework during mesophase formation. This incorporation process produces a mesophase framework that can be activated to form carbons with high crystallinity, thereby enhancing electronic conductivity and hierarchical porosity, which improves ionic conductivity. The resulting carbon electrode is used to assemble a symmetric EDLC, which exhibits a capacitance of 160 F g-1 and excellent high-rate retention in a propylene carbonate solution of N,N-diethyl-N-methylethanaminium tetrafluoroborate. The EDLC delivers a superior specific energy of 40 Wh kg-1 (based on the total carbon mass) within a voltage range of 0-2.7 V and sustained a high energy of 24 Wh kg-1 at a high power of 50 kW kg-1. The findings of this study demonstrate that incorporating aliphatic species into aromatic mesophase frameworks plays a crucial role in regulating the crystallinity and pore structure of pitch-derived carbons for charge storage.
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Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1α expression in tumor tissues. When combined with photodynamic therapy, HIF1α siRNA nanoparticles enhanced the regression in tumor size resulting in a ~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1α siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1α siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma.
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Carcinoma de Células Escamosas/terapia , Terapia Genética/métodos , Neoplasias de Cabeza y Cuello/terapia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias de la Boca/terapia , Nanopartículas , Fotoquimioterapia , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Animales , Apoptosis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Terapia Combinada , Femenino , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Ratones Desnudos , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , ARN Interferente Pequeño/genética , Receptores sigma/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Factores de Tiempo , Transfección , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter â¼25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of (111)In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted (111)In-LCP preferentially accumulated in the lymph nodes at â¼70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only â¼25% ID/g. Larger LCP (diameter â¼67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected (111)In-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed.
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Fosfatos de Calcio , Radioisótopos de Indio , Lípidos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Nanopartículas , Animales , Fosfatos de Calcio/química , Femenino , Lípidos/química , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Nanopartículas/química , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Immunotherapy has shown the potential to become an essential component of the successful treatment of various malignancies. In many cases, such as in melanoma, however, induction of a potent and specific T-cell response against the endogenous antigen or self-antigen still remains a major challenge. To induce a potent MHC I-restricted cytotoxic T-lymphocyte (CTL) response, cytosol delivery of an exogenous antigen into dendritic cells is preferred, if not required. Lipid-calcium-phosphate (LCP) nanoparticles represent a new class of intracellular delivery systems for impermeable drugs. We are interested in exploring the potential of LCP NPs for use as a peptide vaccine delivery system for cancer therapy. To increase the encapsulation of Trp2 peptide into the calcium phosphate precipitate core of LCP, two phosphor-serine residues were added to the N-terminal of the peptide (p-Trp2). CpG ODN was also co-encapsulated with p-Trp2 as an adjuvant. The NPs were further modified with mannose to enhance and prolong the cargo deposit into the lymph nodes (LNs), which ensured persistent antigen loading and stimulation. Compared with free Trp2 peptide/CpG, vaccination with LCP encapsulating p-Trp2 and CpG resulted in superior inhibition of tumor growth in both B16F10 subcutaneous and lung metastasis models. An IFN-γ production assay and in vivo CTL response study revealed that the improved efficacy was a result of a Trp2-specific immune response. Thus, encapsulation of phospho-peptide antigens into LCP may be a promising strategy for enhancing the immunogenicity of poorly immunogenic self-antigens for cancer therapy.
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Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Melanoma/terapia , Proteínas de la Membrana/administración & dosificación , Oligodesoxirribonucleótidos/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Neoplasias Cutáneas/terapia , Adyuvantes Inmunológicos/uso terapéutico , Animales , Fosfatos de Calcio/química , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Femenino , Inmunoterapia , Lípidos/química , Pulmón/inmunología , Pulmón/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Manosa/química , Melanoma/inmunología , Melanoma/patología , Proteínas de la Membrana/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Nanopartículas/química , Nanopartículas/ultraestructura , Oligodesoxirribonucleótidos/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Neoplasias Cutáneas/patología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
To address the question of how cells respond to the possible Ca(2+) toxicity caused by the release of Ca(2+) into the cytoplasm by LCP nanoparticles, a series of in vitro and in vivo studies using Ca(2+) pump inhibitors were conducted. The results indicated that two major Ca(2+) pumps on the plasma membrane and the mitochondrial membrane, respectively, were able to rapidly respond to the elevated cytosolic Ca(2+) concentration and prevent Ca(2+)-induced apoptosis or necrosis. However, exposure to specific inhibitors of calcium pumps would cause LCP-treated H460 cells to undergo necrosis both in vitro and in vivo. These results demonstrated that the Ca(2+) delivered by LCP was not toxic to cells when the cells contain functional Ca(2+) pumps.
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Calcio/efectos adversos , Nanopartículas/efectos adversos , Nanopartículas/química , Animales , Línea Celular Tumoral , Humanos , Ratones , Ratones DesnudosRESUMEN
PURPOSE: The biodistribution of Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) in tumor-bearing mice was investigated using fluorescence imaging. A quantitative validation of this method was done by (3)H and (111)In labeling of the nanoparticles. METHODS: The biodistribution of LCP NPs containing oligonucleotides was investigated using three different probes: Texas-Red labeled oligonucleotides, (3)H-labeled oligonucleotides, and (111)In-labled calcium phosphate. RESULTS: A discrepancy was found between the radioactivity and the fluorescence signals. Signals from (3)H and (111)In exhibited very similar distribution patterns, suggesting that liver and spleen were the major accumulation sites. However, fluorescence imaging indicated that tumor accumulation was predominant. We further confirmed that the fluorescence signals in both liver and spleen were greatly attenuated compared with those in the tumor due to the intrinsic tissue absorption and scattering. Near-infrared (NIR) dye Cy5.5 also suffered from the same problem, in that the quantitative data from whole organs was dramatically affected by absorption and scattering properties of the tissue. CONCLUSIONS: Careful attention must be paid to the quantification and interpretation of fluorescence imaging measurements when comparing different tissues.
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Neoplasias Pulmonares/diagnóstico , Nanopartículas , Oligonucleótidos , Imagen Óptica , Animales , Fosfatos de Calcio , Fluorescencia , Lípidos , Pulmón/patología , Ratones , Ratones Desnudos , Nanopartículas/química , Oligonucleótidos/química , Imagen Óptica/métodos , Distribución Tisular , Xantenos/químicaRESUMEN
This paper presents an efficient and scalable design for histogram-based bilateral filtering (BF) and joint BF (JBF) by memory reduction methods and architecture design techniques to solve the problems of high memory cost, high computational complexity, high bandwidth, and large range table. The presented memory reduction methods exploit the progressive computing characteristics to reduce the memory cost to 0.003%-0.020%, as compared with the original approach. Furthermore, the architecture design techniques adopt range domain parallelism and take advantage of the computing order and the numerical properties to solve the complexity, bandwidth, and range-table problems. The example design with a 90-nm complementary metal-oxide-semiconductor process can deliver the throughput to 124 Mpixels/s with 356-K gate counts and 23-KB on-chip memory.
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A lipid coated calcium phosphate (LCP) nanoparticle (NP) formulation was developed for efficient delivery of small interfering RNA (siRNA) to a xenograft tumor model by intravenous administration. Based on the previous formulation, liposome-polycation-DNA (LPD), which was a DNA-protamine complex wrapped by cationic liposome followed by post-insertion of PEG, LCP was similar to LPD NP except that the core was replaced by a biodegradable nano-sized calcium phosphate precipitate prepared by using water-in-oil micro-emulsions in which siRNA was entrapped. We hypothesized that after entering the cells, LCP would de-assemble at low pH in the endosome, which would cause endosome swelling and bursting to release the entrapped siRNA. Such a mechanism was demonstrated by the increase of intracellular Ca(2+) concentration as shown by using a calcium specific dye Fura-2. The LCP NP was further modified by post-insertion of polyethylene glycol (PEG) with or without anisamide, a sigma-1 receptor ligand for systemic administration. Luciferase siRNA was used to evaluate the gene silencing effect in H-460 cells which were stably transduced with a luciferase gene. The anisamide modified LCP NP silenced about 70% and 50% of luciferase activity for the tumor cells in culture and those grown in a xenograft model, respectively. The untargeted NP showed a very low silencing effect. The new formulation improved the in vitro silencing effect 3-4 folds compared to the previous LPD formulation, but had a negligible immunotoxicity.
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Fosfatos de Calcio/química , Materiales Biocompatibles Revestidos/química , Portadores de Fármacos/química , Lípidos/química , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , Animales , Calcio/metabolismo , Fosfatos de Calcio/toxicidad , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/toxicidad , Citocinas/inmunología , Portadores de Fármacos/toxicidad , Composición de Medicamentos , Femenino , Silenciador del Gen/efectos de los fármacos , Inyecciones Intravenosas , Lípidos/toxicidad , Luciferasas/genética , Ratones , Ratones Desnudos , Nanopartículas/toxicidad , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Polietilenglicoles/química , Polietilenglicoles/toxicidad , ARN Interferente Pequeño/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
RNAi technology has brought a new category of treatments for various diseases including genetic diseases, viral diseases, and cancer. Despite the great versatility of RNAi that can down regulate almost any protein in the cells, the delicate and precise machinery used for silencing is the same. The major challenge indeed for RNAi-based therapy is the delivery system. In this review, we start with the uniqueness and mechanism of RNAi machinery and the utility of RNAi in therapeutics. Then we discuss the challenges in systemic siRNA delivery by dividing them into two categories-kinetic and physical barriers. At the end, we discuss different strategies to overcome these barriers, especially focusing on the step of endosome escape. Toxicity issues and current successful examples for lipid-based delivery are also included in the review.
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Lípidos/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Sistemas de Liberación de Medicamentos , Endosomas/metabolismo , Enfermedades Genéticas Congénitas/terapia , Humanos , Neoplasias/terapia , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Virosis/terapiaRESUMEN
Lipid-based nanoparticle technology has developed from chemical drug carrier into an efficient multifunctional siRNA tumor targeting delivery system. In this review, we start with an overview of the lipid-based nanomedicine history and the two classes of lipidic vectors for DNA or siRNA delivery. Then we discuss the features of lipid-based nanomedicine that lead to effective tumor targeting and the principles behind. We also discuss nanoparticle surface modification, classes of tumor targeting ligands, and other state-of-the-art strategies for enhancing endosome release primarily focused on lipid-based systems. At the end, we show that multifunctional self-assembled lipid-based nanoparticles could also be versatile delivery vehicles for cancer molecular imaging probes.