RESUMO
Design of terpolymers via copolymerization has emerged as a potential strategy for expanding the family of high-performing donor polymers and boosting the photovoltaic performance of non-fullerene polymer solar cells (PSCs). Herein, double-ester-substituted thiophenes and thienothiophenes are incorporated as third building blocks into the donor polymer PBDB-TF, developing two groups of terpolymers with donor-acceptor 1-donor-acceptor 2 (D-A1-D-A2)-type backbones. An optimum 10% concentration of double-ester-substituted thiophene units in PBDB-TF-T10 downshifts the molecular energy and increases the dielectric constant, and delivers proper miscibility and nanostructure in blends with the high-performing acceptor Y6. These characteristics are designed to synergistically enhance the photovoltage, photocurrent, and efficiency of PSCs. The resulting power conversion efficiency (PCE) of 16.4% surpasses the conventional PBDB-TF/Y6 PSCs, and it is among the best-performing PSCs based on PBDB-TF-derived terpolymers. Gratifyingly, PBDB-TF-T10 does not show significant batch-to-batch variation and it retains high PCEs above 16% in a broad range of molecular weights. This work introduces a facile strategy to easily synthesize terpolymers in combination with Y6 for the attainment of high-performing and reproducible non-fullerene PSCs.
RESUMO
Rationale: The developement of oral targeted therapeutics for obesity and obesity-related diseases is challenging, as these diseases involve multiple lesions distributed throughout the whole body. Herein, we report a successful stragety for targeted oral delivery of bindarit to multiple obesity-related lesions including inflamed adipose tissue, fatty liver and atherosclerotic plaques. Methods: The computer simulation from atomstic to mesoscale was first applied for designing bindarit-loaded nanoparticles (pBIN) and laminarin-modified bindarit-loaded nanoparticles (LApBIN). Then pBIN were suceesfully prepared using a dialysis procedure, and LApBIN were prepared though the interaction bewtween laminarin and pBIN. The physiochemical properties, in vitro and in vivo pharmacokinetics, oral targeting capability and in vivo efficacy of LApBIN in various obesity-related diseases were examined. Results: LApBIN were sucessfully designed and prepared. Following oral administration of LApBIN, the nanoparticles could be sucessully orally adsorbed and translocated to monocytes. Contributed by the recruitment of monocytes to multiple obesity-related lesions, LApBIN successfully delivered bindarit to these lesions, and effectively suppressed inflammation there, which exerted successful preventive effects on high-fat-diet-induced obesity, insulin resistance, fatty liver and atherosclerosis. Conclusions:This strategy could represent a promising approach to develop effective oral treatments for obesity and other metabolic diseases.
Assuntos
Glucanos/farmacologia , Indazóis/farmacologia , Obesidade/prevenção & controle , Propionatos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , Aterosclerose/tratamento farmacológico , Simulação por Computador , Dieta Hiperlipídica/métodos , Fígado Gorduroso/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Nanopartículas/administração & dosagem , Placa Aterosclerótica/tratamento farmacológicoRESUMO
Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of atherosclerosis. However, the application of bindarit (a specific synthetic inhibitor of MCP-1) in atherosclerosis has not been confirmed due to the non-specific distribution profile in vivo. Herein, based on the recruitment of monocytes into atherosclerotic plaques, we successfully delivered bindarit into the interior of atherosclerotic plaques through a yeast-derived microcapsule (YC) mediated biomimetic approach. In this biomimetic approach, bindarit was firstly assembled with polyethyleneimine to form the positively charged nanoparticles (BIN/PEI NPs) via multiple intermolecular forces, and then the obtained BIN/PEI NPs were packed into YCs by electrostatic force-mediated spontaneous deposition. Through an oral adsorption routine similar to yeasts, bindarit loaded YCs (BIN/YCs) were distributed into peripheral blood monocytes after oral administration, and then their targeted delivery to atherosclerotic plaques was successfully performed through monocyte transportation. Correspondingly, oral delivery of bindarit loaded YCs afforded notably potentiated efficacies for inhibiting the MCP-1 and further reducing the recruitment of monocytes into atherosclerotic plaques, and thus presented a good efficacy in preventing the formation of atherosclerotic plaques. These results demonstrated that a 'Trojan horse'-like YC mediated nanomedicine delivery strategy is expected to realize the application of certain potential anti-inflammatory drugs in the treatment of atherosclerosis and is of great significance for the development of novel strategies for atherosclerosis treatment.