title: Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.
abstract: The application of tissue-engineered blood vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.forename: Jiansen
authors.initials: J
authors.lastname: Sun
authors.forename: Mingcan
authors.initials: M
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jingting
authors.initials: J
authors.lastname: Zhou
authors.forename: Yangxiao
authors.initials: Y
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.forename: Ju
authors.initials: J
authors.lastname: Tan
authors.forename: Chuhong
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000071916:AC133 Antigen; D000248:Adenosine Kinase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001808:Blood Vessels / Q000166:cytology*; D002478:Cells, Cultured; D002678:Chimera; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D006023:Glycoproteins / Q000737:chemistry; D064368:Healthy Volunteers; D006801:Humans; D010455:Peptides / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D023822:Tissue Engineering
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D052157:Aptamers, Nucleotide; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat; D034741:RNA, Small Interfering; D013311:Streptozocin; D000248:Adenosine Kinase
keywords: CD133; adenosine kinase; aptamer−siRNA chimeras; diabetes mellitus; tissue-engineered blood vessels