Polymer coated nanodiamonds as gemcitabine prodrug with enzymatic sensitivity for pancreatic cancer treatment
Polymer coated nanodiamonds as gemcitabine prodrug with enzymatic sensitivity for pancreatic cancer treatment作者机构：MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and Engineering Zhejiang University Zhejiang Provincial Key Lab of Ophthalmology Eye Center of the Second Affiliated Hospital School of Medicine Zhejiang University School of Chemistry and Chemical Engineering Huazhong University of Science and Technology Max-Planck Institute for Polymer Research Ulm University
出 版 物：《Progress in Natural Science:Materials International》 (自然科学进展·国际材料(英文))
年 卷 期：2020年第30卷第5期
页 面：711-717页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 0702[理学-物理学]
基 金：Financial support from the National Natural Science Foundation of China (51573160) the Science and Technology Program of Zhejiang Province (Grant No. 2016C04002) the Fundamental Research Funds for the Central Universities (2016QNA4033) the support from EU Horizon 2020 hyperdiamond
主 题：Nanodiamonds Self-assembly Enzyme-sensitive Gemcitabine prodrug
摘 要：The fabrication of Gemcitabine(GEM) prodrug was reported to be an effective method to enhance its pancreatic cancer treatment efficiency. Here, a kind of nanocarbon-based materials, nanodiamond(ND), was selected as the nanocarrier of GEM, owing to its outstanding surface properties and non-cytotoxicity. The polyelectrolytes,polyethyleneimine and polyacrylic acid, were used to self-assemble outside ND surface through electrostatic forces, followed by attachment of polyethylene glycol to address better biocompatibility. GEM was conjugated with an enzyme-sensitive peptide gly-phe-leu-gly to build up the controlled release platform. From characterization results of dynamic laser scattering, zeta potential and transmission electron microscope, the significant improvement of ND stability in physiological condition was proved. Non-cytotoxicity of this functionalized ND carriers and cytotoxicity of the prodrug against Bx PC-3 pancreatic cancer cells were indicated by methylthiazolyl tetrazolium(MTT) assay. In vivo experiments also revealed its superior anticancer effect compared with free GEM treatment. Therefore, the combination of polymer coated NDs with high surface capability and enzymeresponsive intracellular GEM release make it possible to realize higher treatment efficiency on pancreatic tumor therapy.
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