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Objective: To explore the feasibility of Tat peptide decorated gelatin–siloxane nanoparticles carrying the calcitonin gene-related peptide (CGRP) gene to transfect into human cerebral microvascular endothelial cells (hCMEC/D3).Methods: Gelatin–siloxane nanoparticles was prepared with the organic modification method and decorated with Tat peptide,and then conjugated with recombinant plasmid pLXSN-CGRP.The entrapment efficiencies of pLXSN-CGRP incorporated into nanoparticles were evaluated by gel electrophoresis.The nanoparticles conjugated with pLXSN-CGRP was transfected into hCMEC/D3 cells.Flow cytometry analysis was used to evaluate whether the plasmid pLXSN-CGRP loaded in nanoparticles could be internalized into the hCMEC/D3 cells and carry out the quantitative assessment of plasmid-containing hCMEC/D3 cells in vitro.ELISA was performed to detect the level of secreted CGRP in cultured medium and the lasting time.