摘要
糖类化合物对树状大分子的修饰,使得树状大分子成电中性,毒性小,因而糖修饰逐渐成为了可替代传统PEG化修饰降低材料细胞毒性的一种途径。本研究中,我们成功地将第四代聚丙烯亚胺树状大分子(PPI)上部分修饰DOTA螯合剂,并在其剩余末端氨基修饰上两个麦芽糖,形成致密的麦芽糖外壳结构(MALDS),进一步螯合Gd(Ⅲ)离子,得到一种低毒性的MR血池造影剂。体外MTT毒性实验与溶血实验均表明,此种MR血池造影剂细胞毒性低、血液相容性高。并且其不仅有高达10.2mM~(-1)s~(-1)的r_1弛豫率,显著高于常规的G5-Gd(Ⅲ)螯合物(4.84 mM~(-1)s~(-1)),而且体外细胞实验显示其能够被U87MG细胞吞噬,表现出良好的MR造影效果,体内小鼠实验也表明此树状大分子造影剂具有主动脉、肾动脉的MR血池造影效果。
Glycodendrimers have been widely used as a potential substitute for PEGylated dendrimers that can render the dendrimers with neutral surface charge and minimal toxicity.In this paper,the fourth generation poly(propylene imine)(PPI) dendrimers were sequentially modified with DOTA ligands and densely organized maltose shell(MAL DS),followed by chelation of Gd(III) ions to form the dendrimer-Gd complexes(PPI-MAL DS-DOTA(Gd)).In vitro cytotoxicity and hemolysis assays demonstrate that the designed dendrimer-Gd complexes are cytocompatible and hemocompatible in the given concentration range.Magnetic resonance(MR) relaxometry studies revealed that the PPI-MAL DS-DOTA(Gd) complexes had a significantly higher r_1 relaxivity(10.2 mM~(-1)s~(-1)) than the dendrimer-Gd complexes without maltose shell modification(4.84 mM~(-1)s~(-1)).The developed PPI-MAL DS-DOTA(Gd) complexes can be uptaken by cancer cells for MR imaging of cancer cells in vitro,and can be used for MR imaging of aorta and renal artery of animals after intravenous injection.Our results suggest that the developed PPI-MAL DS-DOTA(Gd) complexes could be used as a promising contrast agent for blood pool MR imaging applications.
引文
[1]Ciolkowski,M.;Palecz,B.;Appelhans,D.;Voit,B.;Klajnert,B.;Bryszewska,M.Colloids Surf.,B 2012,95:103-108.
[2]Wen,S.H.;Li,K.G.;Cai,H.D.;Chen,Q.;Shen,M.W.;Huang,Y.P.;Peng,C.;Hou,W.X.;Zhu,M.F.;Zhang,G.X.;Shi,X.Y.Biomaterials,2013,5(34):1570-1580.