title: Inhibition of fibrous dysplasia via blocking Gsα with suramin sodium loaded with an alendronate-conjugated polymeric drug delivery system.
abstract: Suramin sodium (SS), which can directly inhibit the committed step of Gsα activation, seems to be a promising drug for treating fibrous dysplasia (FD). Therefore, how to efficiently deliver SS to the lesion site becomes an urgent problem to be solved. Here a bone-targeted and pH-sensitive drug delivery system was constructed to deliver SS for treating FD with high efficiency. The novel type of bone-targeted cationic hyperbranched poly(amine-ester) (HBPAE) was synthesized by the proton-transfer polymerization of triethanolamine and glycidyl methacrylate, followed by surface carboxyl-modification and then conjugation of an alendronate (ALE) bone-targeting moiety. The resultant Suc-HBPAE-ALE formed nanoparticles in aqueous solution, and SS could be encapsulated into the Suc-HBPAE-ALE nanoparticles via electrostatic attraction. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) assays showed that the SS-loaded nanoparticles had a spherical morphology with a mean diameter of 65 nm. The strong affinity of Suc-HBPAE-ALE nanoparticles to bone was verified by the hydroxyapatite (HA) adsorbing experiment. The therapeutic potential of the SS-loaded Suc-HBPAE-ALE nanoparticles was evaluated via the methylthiazoletetrazolium (MTT) assay and flow cytometry (FCM) analysis against FD cells. The experimental results indicated that the SS-loaded Suc-HBPAE-ALE nanoparticles were a highly promising drug delivery system with high efficiency for inhibiting the proliferation of diseased FD cells.
authors.affiliation: Department of Oral Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China. jianjian60@yahoo.com.
authors.forename: Mingming
authors.initials: M
authors.lastname: Lv
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D019386:Alendronate / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D004983:Ethanolamines / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects; D005357:Fibrous Dysplasia of Bone / Q000188:drug therapy; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000037:antagonists & inhibitors*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013498:Suramin / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D004852:Epoxy Compounds; D004983:Ethanolamines; D008689:Methacrylates; D011073:Polyamines; D011092:Polyethylene Glycols; D013498:Suramin; D017886:Durapatite; C009546:triethanolamine; D019205:GTP-Binding Protein alpha Subunits, Gs; C007870:glycidyl methacrylate; D019386:Alendronate