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• W2899641004 abstract "Pulmonary vascular disease encompasses a wide range of serious afflictions with important clinical implications. There is critical need for the development of efficient, nonviral gene therapy delivery systems. Here, a promising avenue to overcome critical issues in efficient cell targeting within the lung via a uniquely designed nanosystem is reported. Polyplexes are created by functionalizing hyperbranched polyethylenimine (PEI) with biological fatty acids and carboxylate-terminated poly(ethylene glycol) (PEG) through a one-pot 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide reaction. Following intravenous injection, polyplexes show an exceptionally high specificity to the pulmonary microvascular endothelium, allowing for the successful delivery of stabilized enhanced green fluorescent protein (eGFP) expressing messenger ribonucleic acid (mRNA). It is further shown, quantitatively, that positive surface charge is the main mechanism behind such high targeting efficiency for these polyplexes. Live in vivo imaging, flow cytometry of single cell suspensions, and confocal microscopy are used to demonstrate that positive polyplexes are enriched in the lung tissue and disseminated in 85–90% of the alveolar capillary endothelium, whilst being sparse in large vessels. Charge modification, achieved through poly(acrylic acid) or heparin coating, drives a highly significant reduction in both targeting percentage and targeting strength, highlighting the importance of specific surface charge, derived from chemical formulation, for efficient targeting of the pulmonary microvascular endothelium." @default.
• W2899641004 created "2018-11-16" @default.
• W2899641004 creator A5001517127 @default.
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• W2899641004 date "2018-11-06" @default.
• W2899641004 modified "2023-10-12" @default.
• W2899641004 title "Highly Efficient In Vivo Targeting of the Pulmonary Endothelium Using Novel Modifications of Polyethylenimine: An Importance of Charge" @default.
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• W2899641004 doi "https://doi.org/10.1002/adhm.201800876" @default.
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