title: Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.
abstract: Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.
authors.affiliation: Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University, Graduate School of Convergence Science and Technology, Suwon, Republic of Korea.
authors.forename: See-Hyoung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University, Graduate School of Convergence Science and Technology, Suwon, Republic of Korea.
authors.forename: Young Ii
authors.initials: YI
authors.lastname: Yoon
authors.affiliation: Department of Radiology, Seoul National University, Bundang Hospital, Seungnam, Republic of Korea.
authors.forename: Hyoungwon
authors.initials: H
authors.lastname: Moon
authors.affiliation: Department of Cellular and Molecular Biology, California State University, Chico, CA, USA.
authors.forename: Ga-Hyun
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Ajou University, Suwon, Republic of Korea.
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University, Graduate School of Convergence Science and Technology, Suwon, Republic of Korea.
authors.forename: Hak Jong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004337:Drug Carriers / Q000627:therapeutic use*; D006657:Histones / Q000378:metabolism; D006801:Humans; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism*; D008081:Liposomes / Q000627:therapeutic use; D045423:Microbubbles / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004337:Drug Carriers; C468783:H2AX protein, human; D006657:Histones; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D008081:Liposomes; D010455:Peptides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin