Department of Engineering, University of Messina, Contrada Di Dio, I-98166 Messina, Italy.
Department of Engineering, University of Messina, Contrada Di Dio, I-98166 Messina, Italy.
Int J Pharm. 2017 Feb 25;518(1-2):185-192. doi: 10.1016/j.ijpharm.2016.12.060. Epub 2017 Jan 2.
A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells.
这里报道了一种基于生物相容且可追踪细胞的药物传递系统——石墨烯量子点（GQD），用于将 DNA 嵌入药物阿霉素（DOX）靶向递送至癌细胞。通过多壁碳纳米管（MWCNT）的酸性氧化和剥落合成了高度分散且水溶性的 GQD，并将其与肿瘤靶向模块生物素（BTN）共价连接，能够有效识别癌细胞上过表达的生物素受体，并负载 DOX。在 A549 细胞上进行的生物学测试报告表明，合成载体（GQD 和 GQD-BTN）的毒性非常低。在 GQD-BTN-DOX 处理的癌细胞中，细胞毒性强烈依赖于细胞摄取，与用缺乏靶向模块 BTN 的相同系统（GQD-DOX）或单独使用游离药物处理的细胞相比，用 GQD-BTN-DOX 系统处理的细胞摄取量更大且延迟。由于癌细胞酸性环境引发药物从纳米系统中脱离，导致药物的核内化延迟。
