Tecnológico Nacional de México/I.T. de Tijuana, Centro de Graduados e Investigación en Química, A.P. 1166, C.P. 22000 Tijuana, B.C., Mexico.
Cátedras CONACYT-Tecnológico Nacional de México/I.T. de Tijuana, Centro de Graduados e Investigación en Química, A.P. 1166, C.P. 22000, Tijuana, B.C., Mexico.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110365. doi: 10.1016/j.colsurfb.2019.110365. Epub 2019 Jul 15.
Stimuli-responsive polymeric nanogels have been proposed as nanocarriers of cisplatin to maximize its effect for cancer treatment. In this work, a comparative study between anionic core nanogels (ACN) and cationic core nanogels (CCN), both with PEGylated shells, has been performed. The nanogels were synthesized with different cross-linked cores: CCN with poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and ACN with poly(2-methacryloyloxi benzoic acid) (P2MBA). Cisplatin chelate formation with carboxylic acids (ACN) or metal coordination with the amine groups (CCN) leads to a high loading of cisplatin into the nanocarriers. The nanocarriers ability to contain and modulate the supply of cisplatin was tested according to the pH of the medium, in which ACN efficiently released the drug at a typical pH value of a tumor tissue (pH = 6.8) while CCN only releases the drug at more acidic, endosome like, conditions (pH = 5). The effect of drug-free nanogels on cell lines NCI-H1437 (non-small cell lung carcinoma) was evaluated, showing biocompatibility at all concentrations studied (30-400 μg/mL) for both ACN and CCN. However, the survival percentage of the cells in contact with cisplatin-loaded nanogels were dependent on the dose, the time of contact and the type of nanogel. Cisplatin loaded CCN induced lower cell viability after 48 h of contact. Fluorescence microscopy showed a viable internalization of the CCN nanogels, this was confirmed by flow cytometry in which 37.8% of cells contained drug loaded CCNs after 30 min of contact, representing a more effective nanocarrier for cisplatin to this cell-line.
刺激响应性聚合物纳米凝胶已被提议作为顺铂的纳米载体，以最大限度地提高其在癌症治疗中的效果。在这项工作中，对带负电荷的核纳米凝胶 (ACN) 和带正电荷的核纳米凝胶 (CCN) 进行了比较研究，这两种纳米凝胶都带有聚乙二醇化外壳。纳米凝胶的交联核不同：CCN 带有聚 (N,N-二乙基氨乙基甲基丙烯酸酯) (PDEAEMA)，ACN 带有聚 (2-甲基丙烯酰氧基苯甲酸) (P2MBA)。与羧酸 (ACN) 形成顺铂螯合物或与胺基配位 (CCN) 导致顺铂高负载纳米载体。根据介质的 pH 值，测试了纳米载体包含和调节顺铂供应的能力，其中 ACN 在肿瘤组织的典型 pH 值 (pH=6.8) 下有效地释放药物，而 CCN 仅在更酸性、类似内涵体的条件 (pH=5) 下释放药物。评估了无药物纳米凝胶对 NCI-H1437 细胞系 (非小细胞肺癌) 的影响，结果表明，在所有研究浓度 (30-400μg/mL) 下，ACN 和 CCN 均具有生物相容性。然而，与载药纳米凝胶接触的细胞的存活率取决于剂量、接触时间和纳米凝胶的类型。载顺铂的 CCN 在接触 48 小时后诱导更低的细胞活力。荧光显微镜显示 CCN 纳米凝胶的活内化，这通过流式细胞术得到证实，其中接触 30 分钟后，37.8%的细胞含有载药的 CCN，这表明 CCN 纳米凝胶是该细胞系中更有效的顺铂纳米载体。
