title: A Heparan Sulfate-Binding Cell Penetrating Peptide for Tumor Targeting and Migration Inhibition.
abstract: As heparan sulfate proteoglycans (HSPGs) are known as co-receptors to interact with numerous growth factors and then modulate downstream biological activities, overexpression of HS/HSPG on cell surface acts as an increasingly reliable prognostic factor in tumor progression. Cell penetrating peptides (CPPs) are short-chain peptides developed as functionalized vectors for delivery approaches of impermeable agents. On cell surface negatively charged HS provides the initial attachment of basic CPPs by electrostatic interaction, leading to multiple cellular effects. Here a functional peptide (CPPecp) has been identified from critical HS binding region in hRNase3, a unique RNase family member with in vitro antitumor activity. In this study we analyze a set of HS-binding CPPs derived from natural proteins including CPPecp. In addition to cellular binding and internalization, CPPecp demonstrated multiple functions including strong binding activity to tumor cell surface with higher HS expression, significant inhibitory effects on cancer cell migration, and suppression of angiogenesis in vitro and in vivo. Moreover, different from conventional highly basic CPPs, CPPecp facilitated magnetic nanoparticle to selectively target tumor site in vivo. Therefore, CPPecp could engage its capacity to be developed as biomaterials for diagnostic imaging agent, therapeutic supplement, or functionalized vector for drug delivery.
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Chien-Jung
authors.identifier: 0000-0003-0926-6342
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Kang-Chiao
authors.identifier: 0000-0002-1693-1462
authors.initials: KC
authors.lastname: Tsai
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Ping-Hsueh
authors.initials: PH
authors.lastname: Kuo
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Chang
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan ; Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan ; Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan ; Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Margaret Dah-Tsyr
authors.initials: MD
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D047150:Eosinophil Cationic Protein / Q000737:chemistry / Q000378:metabolism; D006497:Heparan Sulfate / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D057846:Cell-Penetrating Peptides; D047150:Eosinophil Cationic Protein; D006497:Heparan Sulfate; C479220:RNASE3 protein, human