pH-sensitive nanogels with ortho ester linkages prepared via thiol-ene click chemistry for efficient intracellular drug release
pH-sensitive nanogels with ortho ester linkages prepared via thiol-ene click chemistry for efficient intracellular drug release
复制标题
通过硫醇-烯点击化学制备具有原酸酯键的 pH 敏感纳米凝胶，用于有效的细胞内药物释放
DOI：
10.1016/j.jcis.2017.08.051
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发表时间：
2017
影响因子：
9.9
通讯作者：
Tang Rupei
中科院分区：
文献类型：
--
作者：
Wang Jun;Wang Xin;Yan Guoqing;Fu Shengxiang;Tang Rupei
通过硫醇-烯点击化学反应，方便地制备了具有原酸酯键的pH敏感性纳米凝胶。通过调节原酸酯双丙烯酰胺（OEAM）、季戊四醇四（3-巯基丙酸酯）（PT）和甲氧基聚乙二醇丙烯酸酯（mPEGA）的投料比和浓度，可以将纳米凝胶的粒径控制在100-200 nm，且粒径分布相对较窄。通过核磁共振（NMR）、傅里叶变换红外光谱（FT-IR）、动态激光散射（DLS）和透射电子显微镜（TEM）对纳米凝胶进行了表征。阿霉素（DOX）在NG中的载药率高达73.7%，体外释药实验表明，在pH 5.0时，NG中DOX的原酸酯水解作用使DOX在24 h内释放75.9%。细胞摄取研究证实，DOX负载的NG（NG/DOX）可以很容易地被二维细胞内化，导致癌细胞的有效抗肿瘤效率。采用三维多细胞肿瘤球体（MCTS）作为体外肿瘤模型，进一步评价NG/DOX的抗肿瘤作用。结果表明，与游离DOX相比，NG/DOX在3D多细胞肿瘤球体（MCTS）中显示出显著增强的渗透和生长抑制。
pH-sensitive nanogels with ortho ester linkages were conveniently prepared through reaction of thiol-ene click chemistry. Through adjusting feed reactant ratios and concentrations of ortho ester diacrylamide (OEAM), pentaerythritol tetra(3-mercaptopropionate) (PT), and methoxyl poly(ethyleneglycol) acrylate (mPEGA), the size of the nanogels could be controlled at 100–200 nm with relatively narrow size distributions. The nanogels with size of 149.1 ± 17.7 nm (designed as NG) were verified by proton nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), dynamic laser scattering (DLS) and transmission electron microscopy (TEM). Doxorubicin (DOX) was loaded into NG with high drug loading efficiency up to 73.7%.In vitrodrug release studies showed that up to 75.9% DOX from NG was released in 24 h at pH 5.0 because of hydrolysis of ortho ester. Cellular uptake studies confirmed that DOX-loaded NG (NG/DOX) could be readily internalized by two-dimensional cells, resulting in efficient antitumor efficiency of cancer cells. Three-dimensional (3D) multicellular tumor spheroids (MCTS) asin vitrotumor model was used to further evaluate the antitumor effect of NG/DOX. The results demonstrated that NG/DOX showed a significantly enhanced penetration and growth inhibition in 3D multicellular tumor spheroids (MCTS), compared to free DOX.