title: Targeted Ultrasound-Triggered Phase Transition Nanodroplets for Her2-Overexpressing Breast Cancer Diagnosis and Gene Transfection.
abstract: For successful gene therapy, it is imperative to accumulate therapeutic gene in tumor tissues followed by efficiently delivering gene into targeted cells. Ultrasound irradiation, as a noninvasive and cost-effective external stimulus, has been proved to be one of the most potential external-stimulating gene delivery strategies recently in further improving gene transfection. In this study, we developed tumor-targeting ultrasound-triggered phase-transition nanodroplets AHNP-PFP-TNDs comprising a perfluorinated poly(amino acid) C11F17-PAsp (DET) as a core for simultaneously loading perfluoropentane (PFP) and nucleic acids, and a polyanionic polymer PGA-g-PEG-AHNP as the shell for not only modifying the surface of nanodroplets but also introducing an anti-Her2/neu peptide (AHNP) aiming to targeted treatment of Her2-overexpressing breast cancer. The results showed the average diameter of AHNP-PFP-TNDs was below 400 nm, nearly spherical in shape. The modification of PGA-g-PEG-AHNP not only increased the serum stability of the nanodroplets but also improved the affinity between nanodroplets and Her2-overexpressing breast cells. Both intratumor and intravenous injection of AHNP-PFP-TNDs into nude mice bearing HGC-27 xenografts showed that the gene transfection efficiency and the ultrasound contrast effect were significantly enhanced after exposed to the ultrasound irradiation with optimized ultrasound parameters. Therefore, this targeting nanodroplets system could be served as a potential theranostic vector for tumor targeting ultrasound diagnosis and gene therapy.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Di
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong 510080, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong 510080, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Yingqin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong 510080, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Jie
authors.identifier: 0000-0001-6035-0131
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009696:Nucleic Acids / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D044367:Phase Transition; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014463:Ultrasonography / Q000379:methods; D010420:Pentanes
chemical_list: D005466:Fluorocarbons; D009696:Nucleic Acids; D010455:Peptides; D000071228:Polyelectrolytes; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; C008806:perfluoropentane; D010420:Pentanes
keywords: Her2 targeting; cavitation; gene delivery; perfluoropentane; ultrasound irradiation