title: A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro.
abstract: Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MBiRGD/CCR2) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MBiRGD/CCR2 had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MBiRGD/CCR2 had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MBiRGD or MBCCR2) (P < 0.05 for both). Agarose gel electrophoresis assay showed that MBiRGD/CCR2 can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MBcontrol) or single-targeted cationic MBs including MBiRGD and MBCCR2 (P < 0.05 for all), the dual-targeted cationic MBiRGD/CCR2 groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MBiRGD/CCR2 has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy.
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China. maggielyy21064@163.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Zhanghong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Ultrasonography, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: The Department of Echocardiography, Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, 571101, China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Tan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. fei.yan@siat.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
mesh_terms: D003287:Contrast Media; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D045423:Microbubbles; D010957:Plasmids / Q000008:administration & dosage; D014162:Transfection; D014465:Ultrasonics
chemical_list: D003287:Contrast Media; D049452:Green Fluorescent Proteins
keywords: Dual-targeted; Gene delivery; Microbubbles; Ultrasound