title: Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.
abstract: A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.
authors.affiliation: a Department of Clinical Laboratory , Huangshi Love & Health Hospital of Hubei Province , Huangshi , People's Republic of China .
authors.forename: Wen
authors.initials: W
authors.lastname: Lin
authors.affiliation: b Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , People's Republic of China , and.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: a Department of Clinical Laboratory , Huangshi Love & Health Hospital of Hubei Province , Huangshi , People's Republic of China .
authors.forename: Jianping
authors.initials: J
authors.lastname: Deng
authors.affiliation: b Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , People's Republic of China , and.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: b Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , People's Republic of China , and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: b Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , People's Republic of China , and.
authors.forename: Xudong
authors.initials: X
authors.lastname: Fu
authors.affiliation: b Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , People's Republic of China , and.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: c Department of Pharmacy , Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D009842:Oligopeptides / Q000008:administration & dosage*; D014465:Ultrasonics / Q000379:methods
chemical_list: D057846:Cell-Penetrating Peptides; C526428:NGR peptide; D009842:Oligopeptides; D004317:Doxorubicin
keywords: Cell-penetrating peptides; NGR-targeted; drug delivery; nanobubbles; ultrasound