Fluorinated amphiphilic Poly(β-Amino ester)nanoparticle for highly efficient and specific delivery of nucleic acids to the Lung capillary endothelium

作     者：Zicheng Deng Wen Gao Fatemeh Kohram Enhong Li Tanya V.Kalin Donglu Shi Vladimir V.Kalinichenko 

作者机构：Phoenix Children’s Health Research InstituteDepartment of Child HealthUniversity of Arizona College of Medicine-PhoenixPhoenixAZ85004USA Division of Pulmonary BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH45229USA The Materials Science and Engineering ProgramCollege of Engineering and Applied ScienceUniversity of CincinnatiCincinnatiOH45221USA Division of NeonatologyPhoenix Children’s HospitalPhoenixAZ85016USA 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2024年第31卷第1期

页      面：1-17页

核心收录：

学科分类：07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 

基　　金：National Institutes of Health  NIH 

主　　题：Poly(β-amino)esters nanoparticle Lung microvascular endothelium Gene delivery Specific targeting 

摘      要：Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension,viral and bacterial pneumonia,bronchopulmonary dysplasia,and congenital lung diseases such as alveolar capillary dysplasia with misalignment of pulmonary veins(ACDMPV).To correct endothelial dysfunction,there is a critical need for the development of nanoparticle systems that can deliver drugs and nucleic acids to endothelial cells with high efficiency and *** several nanoparticle delivery systems targeting endothelial cells have been recently developed,none of them are specific to lung endothelial cells without targeting other organs in the *** the present study,we successfully solved this problem by developing non-toxic poly(β-amino)ester(PBAE)nanoparticles with specific structure design and fluorinated modification for high efficiency and specific delivery of nucleic acids to the pulmonary endothelial *** intravenous administration,the PBAE nanoparticles were capable of delivering non-integrating DNA plasmids to lung microvascular endothelial cells but not to other lung cell *** whole body imaging and flow cytometry demonstrated that DNA plasmid were functional in the lung endothelial cells but not in endothelial cells of other *** of PBAE was required for lung endothelial cell-specific *** analysis and liver and kidney metabolic panels demonstrated the lack of toxicity in experimental ***,fluorinated PBAE nanoparticles can be an ideal vehicle for gene therapy targeting lung microvascular endothelium in pulmonary vascular disorders.