CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal.
Biomacromolecules. 2013 Sep 9;14(9):3140-6. doi: 10.1021/bm400768m. Epub 2013 Aug 22.
Although doxorubicin (Dox) has been widely used in the treatment of different types of cancer, its insufficient cellular uptake and intracellular release is still a limitation. Herein, we report an easy process for the preparation of redox-sensitive nanogels that were shown to be highly efficient in the intracellular delivery of Dox. The nanogels (AG/Cys) were obtained through in situ cross-linking of alginate (AG) using cystamine (Cys) as a cross-linker via a miniemulsion method. Dox was loaded into the AG/Cys nanogels by simply mixing it in aqueous solution with the nanogels, that is, by the establishment of electrostatic interactions between the anionic AG and the cationic Dox. The results demonstrated that the AG/Cys nanogels are cytocompatible, have a high drug encapsulation efficiency (95.2 ± 4.7%), show an in vitro accelerated release of Dox in conditions that mimic the intracellular reductive conditions, and can quickly be taken up by CAL-72 cells (an osteosarcoma cell line), resulting in higher Dox intracellular accumulation and a remarkable cell death extension when compared with free Dox. The developed nanogels can be used as a tool to overcome the problem of Dox resistance in anticancer treatments and possibly be used for the delivery of other cationic drugs in applications beyond cancer.
尽管多柔比星（Dox）已被广泛用于治疗不同类型的癌症，但它的细胞摄取和细胞内释放不足仍然是一个限制。在此，我们报告了一种制备氧化还原敏感纳米凝胶的简便方法，该纳米凝胶在多柔比星的细胞内递送中显示出很高的效率。纳米凝胶（AG/Cys）是通过使用半胱胺（Cys）作为交联剂，通过 miniemulsion 方法原位交联海藻酸钠（AG）而获得的。通过将多柔比星简单地混合在含有纳米凝胶的水溶液中，即通过阴离子 AG 与阳离子多柔比星之间的静电相互作用，将多柔比星载入 AG/Cys 纳米凝胶中。结果表明，AG/Cys 纳米凝胶具有细胞相容性，药物包封效率高（95.2±4.7%），在模拟细胞内还原条件下，多柔比星表现出体外加速释放，并且可以被 CAL-72 细胞（骨肉瘤细胞系）快速摄取，与游离多柔比星相比，多柔比星在细胞内的积累更高，细胞死亡延长显著。开发的纳米凝胶可用作克服癌症治疗中多柔比星耐药性的工具，并且可能用于除癌症以外的其他阳离子药物的递送。
