Delivery of Amonafide from Fructose-Coated Nanodiamonds by Oxime Ligation for the Treatment of Human Breast Cancer.
Delivery of Amonafide from Fructose-Coated Nanodiamonds by Oxime Ligation for the Treatment of Human Breast Cancer.
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DOI：
10.1021/acs.biomac.7b01592
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发表时间：
2018-01
影响因子：
6.2
通讯作者：
Jiacheng Zhao;Mingxia Lu;H. Lai;Hongxu Lu;J. Lalevée;C. Barner‐Kowollik;M. Stenzel;P. Xiao
中科院分区：
文献类型：
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作者：
Jiacheng Zhao;Mingxia Lu;H. Lai;Hongxu Lu;J. Lalevée;C. Barner‐Kowollik;M. Stenzel;P. Xiao
引入一种具有高聚合物接枝密度和可访问的聚合物结构表征的聚合物/纳米金刚石杂化物的策略对于纳米金刚石的表面改性和生物制剂附着以用于其生物医学应用是至关重要的。在这里，我们报告了一个二元共聚物/纳米金刚石杂化药物传递系统，这是通过接枝amonafide共轭二元共聚物到纳米金刚石表面通过肟连接制备。通过RAFT聚合制备了侧链含醛基的聚（1-O-甲基丙烯酰基-2，3：4，5-二-O-异亚丙基-β-d-吡喃果糖）-b-聚（3-乙烯基苯并呋喃-co-甲基丙烯酸甲酯）。抗癌药物氨萘非通过亚胺化学与聚合物链结合，产生酸可降解的亚胺键。随后通过肟连接将所获得的氨萘非缀合的二元共聚物接枝到氨氧基官能化的纳米金刚石的表面上。共轭聚合物的分子量通过尺寸排阻色谱（SEC）表征，而成功的共轭和相应的接枝密度通过核磁共振（NMR）、傅里叶变换红外光谱（FTIR）和热重分析（TGA）评估。我们的研究结果表明，amonafide在聚合物链中的质量百分比约为17%，聚合物链的表面密度为0.24分子/nm 2。所制备的药物递送系统具有约380 nm的流体动力学尺寸，具有低PDI（0.3），并且可以有效地将氨萘非递送到乳腺癌细胞中并显著抑制癌细胞活力。在2D细胞培养模型中，ND-聚合物-AMF递送系统的IC 50值（MCF-7为7.19 μM; MDA-MB-231为4.92 μM）低于游离氨萘非的IC 50值（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/聚合物递送系统的抑制的细胞活力，这表明聚合物-金刚石杂化材料可以是用于乳腺癌治疗的有希望的平台。
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/nm2. 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 IC50 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.