Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Nanomedicine. 2018 Jun;14(4):1181-1190. doi: 10.1016/j.nano.2018.02.002. Epub 2018 Feb 17.
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors. Functionalized DNA nanocages are highly stable, not cytotoxic and can be efficiently loaded with the chemotherapeutic agent doxorubicin. After entry into cells, doxorubicin-loaded nanoparticles are confined in vesicular structures, indicating that DNA nanocages traffic through the endocytic pathway. Doxorubicin release from loaded DNA cages, facilitated by low pH of endocytic vesicles, induces toxic pathways that, besides selectively killing folate receptor-positive cancer cells, leads to cage degradation avoiding nanoparticles accumulation inside cells.
选择性靶向是用于癌症治疗药物递送的纳米载体的一个关键特性。我们通过生物正交共轭化学生成了生物素化的具有叶酸功能化的八面体 DNA 纳米笼。分子建模表明，叶酸和 DNA 纳米笼之间约 2.5nm 的距离可以避免与叶酸受体的空间位阻。HeLa 细胞，一种叶酸受体阳性肿瘤细胞系，比不表达叶酸受体的细胞对叶酸-DNA 纳米笼的内化效率高 40 多倍。功能化的 DNA 纳米笼具有高度稳定性，无细胞毒性，并且可以有效地装载化疗药物阿霉素。进入细胞后，载有阿霉素的纳米颗粒被限制在囊泡结构中，表明 DNA 纳米笼通过内吞途径运输。通过内吞小泡的低 pH 值促进负载 DNA 笼的阿霉素释放，诱导毒性途径，除了选择性杀死叶酸受体阳性癌细胞外，还导致笼降解，避免纳米颗粒在细胞内积累。
