Centre for Advanced Macromolecular Design, School of Chemistry, The University of New South Wales , Sydney, New South Wales 2052, Australia.
Institut de Science des Matériaux de Mulhouse IS2M, UMR CNRS 7361, ENSCMu-UHA, 15, rue Jean Starcky, 68057 Mulhouse Cedex, France.
Biomacromolecules. 2018 Feb 12;19(2):481-489. doi: 10.1021/acs.biomac.7b01592. Epub 2018 Jan 23.
The introduction of a strategy toward polymer/nanodiamond hybrids with high polymer grafting density and accessible polymer structural characterization is of critical importance for nanodiamonds' surface modification and bioagent attachment for their biomedical application. Here, we report a glycopolymer/nanodiamond hybrid drug delivery system, which was prepared by grafting amonafide-conjugated glycopolymers onto the surface of nanodiamonds via oxime ligation. Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose)-b-poly(3-vinylbenzaldehyde-co-methyl methacrylate), featuring pendant aldehyde groups, is prepared via RAFT polymerization. The anticancer drug amonafide is conjugated to the polymer chains via imine chemistry, resulting in acid-degradable imine linkages. The obtained amonafide-conjugated glycopolymers are subsequently grafted onto the surface of aminooxy-functionalized nanodiamonds via oxime ligation. The molecular weight of the conjugated polymers is characterized by size-exclusion chromatography (SEC), while the successful conjugation and corresponding grafting density is assessed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric aanalysis (TGA). Our results indicate that the mass percentage of amonafide in the polymer chains is around 17% and the surface density of polymer chains is 0.24 molecules/nm. The prepared drug delivery system has a hydrodynamic size around 380 nm with low PDI (0.3) and can effectively deliver amonafide into breast cancer cell and significantly inhibit the cancer cell viability. In 2D cell culture models, the IC values of ND-Polymer-AMF delivery system (7.19 μM for MCF-7; 4.92 μM for MDA-MB-231) are lower than those of free amonafide (11.23 μM for MCF-7; 13.98 μM for MDA-MB-231). An inhibited cell viability of nanodiamonds/polymer delivery system is also observed in 3D spheroids' models, suggesting that polymer-diamonds hybrid materials can be promising platforms for breast cancer therapy.
引入一种具有高聚合物接枝密度和可访问聚合物结构表征的聚合物/纳米金刚石杂化策略对于纳米金刚石的表面改性和生物制剂附着至关重要，以实现其在生物医学中的应用。在这里，我们报告了一种糖聚合物/纳米金刚石杂化药物递送系统，该系统是通过肟键将接枝有单氟酰胺的糖聚合物接枝到纳米金刚石表面而制备的。聚（1-O-甲基丙烯酰基-2,3:4,5-二-O-亚异丙基-β-d-呋喃果糖基）-b-聚（3-乙烯基苯甲醛-co-甲基甲基丙烯酸甲酯），具有末端醛基，通过 RAFT 聚合制备。抗癌药物单氟酰胺通过亚胺化学连接到聚合物链上，导致酸可降解的亚胺键。所得的接枝有单氟酰胺的糖聚合物随后通过肟键接枝到氨氧基功能化的纳米金刚石表面。通过凝胶渗透色谱（SEC）对共轭聚合物的分子量进行了表征，而通过核磁共振（NMR）、傅里叶变换红外光谱（FTIR）和热重分析（TGA）评估了成功的接枝和相应的接枝密度。我们的结果表明，聚合物链中单氟酰胺的质量百分比约为 17%，聚合物链的表面密度为 0.24 个分子/nm。制备的药物递送系统的水动力直径约为 380nm，具有低 PD 值（0.3），可以有效地将单氟酰胺递送入乳腺癌细胞，并显著抑制癌细胞活力。在二维细胞培养模型中，ND-聚合物-AMF 递送系统（MCF-7 为 7.19 μM；MDA-MB-231 为 4.92 μM）的 IC 值低于游离单氟酰胺（MCF-7 为 11.23 μM；MDA-MB-231 为 13.98 μM）。在 3D 球体模型中也观察到纳米金刚石/聚合物递送系统抑制细胞活力，这表明聚合物-金刚石杂化材料可能是乳腺癌治疗的有前途的平台。
