title: Novel cell-penetrating peptide-loaded nanobubbles synergized with ultrasound irradiation enhance EGFR siRNA delivery for triple negative Breast cancer therapy.
abstract: The lack of safe and effective gene delivery strategies remains a bottleneck for cancer gene therapy. Here, we describe the synthesis, characterization, and application of cell-penetrating peptide (CPP)-loaded nanobubbles (NBs), which are characterized by their safety, strong penetrating power and high gene loading capability for gene delivery. An epidermal growth factor receptor (EGFR)-targeted small interfering RNA (siEGFR) was transfected into triple negative breast cancer (TNBC) cells via prepared CPP-NBs synergized with ultrasound-targeted microbubble destruction (UTMD) technology. Fluorescence microscopy showed that siEGFR and CPP were loaded on the shells of the NBs. The transfection efficiency and cell proliferation levels were evaluated by FACS and MTT assays, respectively. In addition, in vivo experiments showed that the expression of EGFR mRNA and protein could be efficiently downregulated and that the growth of a xenograft tumor derived from TNBC cells could be inhibited. Our results indicate that CPP-NBs carrying siEGFR could potentially be used as a promising non-viral gene vector that can be synergized with UTMD technology for efficient TNBC therapy.
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.
authors.forename: Shouqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Leng
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Shouping
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: jwtian2004@163.com.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045423:Microbubbles; D036103:Nanotechnology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014465:Ultrasonics; D023041:Xenograft Model Antitumor Assays
chemical_list: D057846:Cell-Penetrating Peptides; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cell-penetrating peptide; Gene transfection; Nanobubbles; Triple negative breast cancer; Ultrasound-targeted microbubble destruction