title: Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound.
abstract: Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA.
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory, Huangshi Love & Health Hospital of Hubei Province, Huangshi, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lin
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China. Electronic address: amms2013@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Huangshi Love & Health Hospital of Hubei Province, Huangshi, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D057846:Cell-Penetrating Peptides; D034741:RNA, Small Interfering
keywords: Cell-penetrating peptides; Nanobubbles; Ultrasound; siRNA delivery