PMID- 37222145 OWN - NLM STAT- MEDLINE DCOM- 20230608 LR - 20230617 IS - 2050-7518 (Electronic) IS - 2050-750X (Linking) VI - 11 IP - 22 DP - 2023 Jun 7 TI - A pDNA/rapamycin nanocomposite coating on interventional balloons for inhibiting neointimal hyperplasia. PG - 4882-4889 LID - 10.1039/d3tb00344b [doi] AB - Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries. FAU - Lai, Yu-Xian AU - Lai YX AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. FAU - Fu, Jia-Yin AU - Fu JY AD - Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. fugs@zju.edu.cn. FAU - Wu, Shao-Fei AU - Wu SF AD - Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. fugs@zju.edu.cn. FAU - Li, Ren-Yun AU - Li RY AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. FAU - Hu, Jia-Qi AU - Hu JQ AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. FAU - Wang, You-Xiang AU - Wang YX AUID- ORCID: 0000-0002-7821-9470 AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. FAU - Martins, M Cristina L AU - Martins MCL AUID- ORCID: 0000-0002-6574-4794 AD - i3S-Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, P-4200-135, Porto, Portugal. FAU - Ren, Ke-Feng AU - Ren KF AUID- ORCID: 0000-0001-5456-984X AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. AD - Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. fugs@zju.edu.cn. FAU - Ji, Jian AU - Ji J AUID- ORCID: 0000-0001-9870-4038 AD - MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. renkf@zju.edu.cn. AD - Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. fugs@zju.edu.cn. FAU - Fu, Guo-Sheng AU - Fu GS AD - Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. fugs@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230607 PL - England TA - J Mater Chem B JT - Journal of materials chemistry. B JID - 101598493 RN - 0 (Vascular Endothelial Growth Factor A) RN - W36ZG6FT64 (Sirolimus) RN - 9007-49-2 (DNA) RN - 0 (Vascular Endothelial Growth Factors) SB - IM MH - Humans MH - *Vascular Endothelial Growth Factor A MH - Sirolimus/pharmacology MH - Hyperplasia/drug therapy MH - *Vascular System Injuries MH - Plasmids MH - DNA MH - Vascular Endothelial Growth Factors EDAT- 2023/05/24 06:42 MHDA- 2023/06/08 06:42 CRDT- 2023/05/24 05:28 PHST- 2023/06/08 06:42 [medline] PHST- 2023/05/24 06:42 [pubmed] PHST- 2023/05/24 05:28 [entrez] AID - 10.1039/d3tb00344b [doi] PST - epublish SO - J Mater Chem B. 2023 Jun 7;11(22):4882-4889. doi: 10.1039/d3tb00344b.