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      Inhibition of fibrous dysplasia via blocking Gsα with suramin sodium loaded with an alendronate-conjugated polymeric drug delivery system.

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          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.

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          Author and article information

          Journal
          Biomater Sci
          Biomaterials science
          Royal Society of Chemistry (RSC)
          2047-4849
          2047-4830
          Jul 21 2016
          : 4
          : 7
          Affiliations
          [1 ] 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.
          Article
          10.1039/c6bm00091f
          27180636
          b1e640c0-0a90-408c-bced-5151e7969bef
          History

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