title: Ultrasound-Triggered Phase-Transition Cationic Nanodroplets for Enhanced Gene Delivery.
abstract: Ultrasound as an external stimulus for enhanced gene transfection represents a safe, noninvasive, cost-effective delivery strategy for gene therapy. Herein, we have developed an ultrasound-triggered phase-transition cationic nanodroplet based on a novel perfluorinated amphiphilic poly(amino acid), which could simultaneously load perfluoropentane (PFP) and nucleic acids. The heptadecafluoroundecylamine (C11F17-NH2) was chosen to initiate β-benzyl-L-aspartate N-carboxyanhydride (BLA-NCA) ring-opening polymerization to prepare C11F17-poly(β-benzyl-L-aspartate) (C11F17-PBLA). Subsequently, C11F17-poly{N-[N'-(2-aminoethyl)]aspartamide} [C11F17-PAsp(DET)] was synthesized by aminolysis reaction of C11F17-PBLA with diethylenetriamine (DET). PFP/pDNA-loaded nanodroplets PFP-TNDs [PFP/C11F17-PAsp(DET)/LucDNA/γ-PGA or poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets] were primarily formulated by an oil/water emulsification method, followed by surface modification with PGA-g-mPEG. The average diameter of PFP-TNDs ranged from 300 to 400 nm, and transmission electron microscopy images showed that the nanodroplets were nearly spherical in shape. The ζ potential of the nanodroplets dramatically decreased from +54.3 to +15.3 mV after modification with PGA-g-mPEG, resulting in a significant increase of the stability of the nanodroplets in the serum-containing condition. With ultrasound irradiation, the gene transfection efficiency was enhanced 14-fold on HepG2 cells, and ultrasound-triggered phase-transition cationic nanodroplets also displayed a good ultrasound contrast effect. These results suggest that the PFP/DNA-loaded phase-transition cationic nanodroplets can be utilized as efficient theranostic agents for targeting gene delivery.
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 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 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 Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Chen
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 Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
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.initials: J
authors.lastname: Liu
mesh_terms: D002412:Cations / Q000737:chemistry / Q000493:pharmacokinetics; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005466:Fluorocarbons / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013010:Sonication / Q000379:methods*; D014162:Transfection / Q000379:methods*; D010420:Pentanes
chemical_list: D002412:Cations; D004247:DNA; D004337:Drug Carriers; D005466:Fluorocarbons; D008156:Luciferases; C008806:perfluoropentane; D010420:Pentanes
keywords: acoustic droplet vaporization; cavitation; gene transfection; nanodroplets; perfluoropentane; ultrasound