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Wise design strategies for efficient ultraviolet (UV) hot exciton molecules are highly desired. In this work, inspired by the long-short axis skeleton strategy, a theoretical study on the substituent effect of the long-axis on the photophysical properties of UV hot exciton molecules is performed. A multiscale simulation is performed to study the photophysical properties of the reported compound 2BuCz-CNCz and theoretically designed promising compounds 2Cz-CNCz, 2TPA-CNCz2TPA-CNCz, 2Na-CNCz and 2An-CNCz, which all possess unique features of UV emission and hot exciton properties. The packing modes of the five molecules in a film are obtained by molecular dynamics (MD) simulations, and then the photophysical properties with the consideration of the SSE (solid-state effect) are studied by using the combined quantum mechanics and molecular mechanics (QM/MM) method. Finally, the exciton evolution process is revealed by the rate equations. The results show that different substituents in the long axis have relatively little effect on the larger twist angle in the short axis. The tert-butyl and triphenylamine groups increase the vibration of the molecule, enhance the non-radiative rate of the molecule and intensify the energy dissipation, but the vibration of tert-butyl can be greatly restrained in the solid state. Furthermore, our designed 2Na-CNCz compound possesses the maximum reverse intersystem crossing rate and radiative decay rate. Therefore, when studying the effect of the long-axis substituents on the properties of hot excitons, 2Na-CNCz could be a profitable candidate molecule. This work should enrich the theoretical calculation methods to investigate the luminescence properties of organic molecules in OLEDs.
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Fluorescent emitters with the hot exciton mechanism combined with aggregation induced emission (AIE) character show prospective applications in organic light emitting diodes (OLEDs). However, theoretical studies on amorphous states are limited. In this work, a theoretical study is performed on the photophysical properties of the reported compound 4-(7-(10-ethyl-10H-phenothiazin-3-yl)benzo[c][1,2,5]thiadiazol-4-yl)-N,N-diphenylaniline (PBTPA), which possesses a hot exciton mechanism and AIE. The aggregation states of this molecule in a film are given by molecular dynamics (MD) simulations, and then the photophysical properties are studied by using the QM/MM method with the consideration of the solid-state effect (SSE). The results explain the hot exciton and AIE mechanism of the molecule. First, there is a hot exciton channel between the S1 and T2 state of the PBTPA. Second, the conformational changes of PBTPA between the ground state and the excited state are restricted in the aggregate state. Last, in the low frequency region, the rotation motion is suppressed, and then the reorganization energy and Huang-Rhys (HR) factor in the aggregate state are much smaller. Therefore, the molecules show strong fluorescence efficiency in the aggregated state.
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Simulación de Dinámica Molecular , RotaciónRESUMEN
Background: Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer. Methods: Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors. Results: Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®. Conclusion: Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.
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Neoplasias de la Mama , Ginsenósidos , Liposomas , Humanos , Femenino , Liposomas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Línea Celular TumoralRESUMEN
PEGylated cholesterol-containing liposomes (Chol-PEG-lipo) have been widely used as a drug carrier for their good stealth property in blood circulation where cholesterol maintains the stability of the liposomal lipid bilayer and PEGylation endows liposomes with long circulation capability. However, cholesterol-related disadvantages and the accelerated blood clearance (ABC) phenomenon caused by PEGylation greatly limit the application of conventional stealth liposomes in clinic. Herein, ginsenoside Rg3 was selected to substitute cholesterol and PEG for liposomes preparation (Rg3-lipo). Rg3 was proved with similar liposomal membrane regulation ability to cholesterol and comparable long circulation effect to PEG. In addition, repeated administrations of Chol-PEG-lipo and Rg3-lipo were performed. The circulation time of the second dose of Chol-PEG-lipo was substantially reduced accompanied by a greatly increased accumulation in the liver due to the induction of anti-PEG IgM and the subsequent activated complement system. In contrast, no significantly increased level of relative plasma cells, IgM secretion and the complement activation in blood circulation was observed after the second injection of Rg3-lipo. As a result, Rg3-lipo showed great stealth property without ABC phenomenon. Therefore, developing liposomes utilizing Rg3 instead of PEG and cholesterol presents a promising strategy to prolong the blood circulation time of liposomes without triggering the ABC phenomenon and activated immune responses.
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Liposomas , Polietilenglicoles , Ratas , Animales , Ratas Wistar , Inmunoglobulina M , ColesterolRESUMEN
Purpose: To compare the clinical features and vitreous biomarkers of proliferative diabetic retinopathy (PDR) between patients with early-onset and late-onset type 2 diabetes mellitus (T2DM). Materials and Methods: This case-control study analyzed the clinical data of 74 patients with PDR who underwent vitrectomy. The patients were divided into the early-onset (T2DM diagnosis age ≤ 40 years, n = 39) and late-onset (T2DM diagnosis age > 40 years, n = 35) groups. Thirty-six specimens were collected, and the liquid chip technology was used to detect the content of 27 types of cytokines in the vitreous. Differences in clinical features and cytokine levels between the two groups were evaluated. Bonferroni correction was applied for multiple comparisons. Results: Compared with the late-onset group, the levels of hemoglobin A1c (HbA1c) and total cholesterol were significantly higher in the early-onset group (P < 0.001 and P = 0.009, respectively). Patients with early-onset T2DM PDR had worse visual prognoses and a higher rate of postoperative recurrent vitreous hemorrhage. The results of cytokine detection showed that the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-9, granulocyte colony-stimulating factor, interferon-γ, interferon-inducible 10 kDa, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß in the early-onset group were significantly higher than those in the late-onset group (p < 0.0026). Age at diabetes diagnosis and HbA1c, IL-4, and regulated upon activation, normal T cell expressed and secreted levels were independent risk factors for visual acuity after undergoing vitrectomy. Conclusion: Early-onset T2DM PDR patients had poor blood glucose and lipid metabolism, higher levels of inflammatory factors, and worse visual prognosis. Stricter metabolic management and earlier anti-inflammatory interventions may be required for patients with early-onset T2DM.