Construction of an Aptamer–SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery
Wen Chen
Wen Zeng
Jiansen Sun
Mingcan Yang
Li Li
Jingting Zhou
Yangxiao Wu
Jun Sun
Ge Liu
Rui Tang
Ju Tan
Chuhong Zhu
10.1021/acsnano.5b01203.s001
https://acs.figshare.com/articles/journal_contribution/Construction_of_an_Aptamer_SiRNA_Chimera_Modified_Tissue_Engineered_Blood_Vessel_for_Cell_Type_Specific_Capture_and_Delivery/2155903
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 <i>in vivo</i> 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 <i>in vivo</i>, 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 HAuCl<sub>4</sub> 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′-<i>O</i>-methyl modification was used to enhance the <i>in vivo</i> 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.
2015-06-23 00:00:00
EPC
RNA transfection
day 30 postgrafting
sustainably releases adenosine
PEG
ADK
vivo
chimera
application
diabetes
PEI
TEBV