title: Synthesis and biological evaluation of a folate-targeted rhaponticin conjugate.
abstract: To improve the therapeutic effect of rhaponticin (RHA), a folate receptor (FR) targeted RHA conjugate was synthesized by utilizing a hydrophilic peptide spacer linked to folic acid (FA) via a releasable disulfide linker. This water-soluble conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Treatment of FRHA with a reducing agent indicated that the amino-reactive derivative of RHA would be released spontaneously following disulfide bond reduction within the endosomes. FRHA also proved to be active predominantly specific against FR-positive syngeneic and xenograft models in vivo, and possible curative activity resulted with minimal to moderate toxicity. The FRHA conjugate greatly enhanced the therapeutic effects and reduced the toxicity of RHA. In conclusion, FRHA represents a folate-targeted chemotherapeutic that can produce potent activity against established sc tumors. Hence, this report has a great significance in pharmacology and clinical medicine as well as methodology.
authors.affiliation: School of Chemical Engineering, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Liang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zeng
authors.forename: Lusha
authors.initials: L
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Ma
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013267:Stilbenes / Q000097:blood / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D058973:Folate Receptors, GPI-Anchored; D013267:Stilbenes; D005492:Folic Acid; C023538:rhapontin