Boncel Sławomir, Herman Artur P, Budniok Sebastian, Jędrysiak Rafał G, Jakóbik-Kolon Agata, Skepper Jeremy N, Müller Karin H
Department of Organic Chemistry, Biochemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, Gliwice 44-100, Poland.
Department of Inorganic Chemistry, Analytical Chemistry and Electrochemistry, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 6, Gliwice 44-100, Poland.
ACS Biomater Sci Eng. 2016 Aug 8;2(8):1273-1285. doi: 10.1021/acsbiomaterials.6b00197. Epub 2016 Jul 19.
Fe-encapsulated multiwall carbon nanotubes (Fe@MWCNTs) are candidates for magnetically targeted Drug Delivery Systems (mt-DDSs) against breast cancer. However, their full potential as versatile and biosafe vectors has yet to be developed. Key challenges that remain are relating surface functionalization to cytotoxicity and inducing selective cytotoxicity to cancer cells. We have studied quantitative uptake of pristine and functionalized Fe@MWCNTs (f-Fe@MWCNTs) in correlation to their cytotoxicity. Human monocyte macrophages (HMMs) and T47D breast cancer cells were selected as models to test selective cytotoxicity. [2+1]-Cycloaddition of nitrenes to Fe@MWCNTs yielded both effective functionalization and drug "tethering". Hydrophilization of Fe@MWCNTs was critical for efficient active cell uptake. f-Fe@MWCNTs were considerably more toxic to T47D cells than HMMs, in spite of longer exposure times of the latter. Eventually, Fe@MWCNTs loaded with 5-fluorouracil in a β-cyclodextrin cage or with covalently linked purpurin emerged as the most cytotoxic and steerable in a magnetic field toward promising mt-DDSs.
铁封装的多壁碳纳米管（Fe@MWCNTs）是用于针对乳腺癌的磁靶向给药系统（mt-DDSs）的候选材料。然而，它们作为通用且生物安全载体的全部潜力尚未得到开发。仍然存在的关键挑战是将表面功能化与细胞毒性相关联，并诱导对癌细胞的选择性细胞毒性。我们研究了原始和功能化的Fe@MWCNTs（f-Fe@MWCNTs）的定量摄取与其细胞毒性的相关性。选择人单核巨噬细胞（HMMs）和T47D乳腺癌细胞作为测试选择性细胞毒性的模型。氮烯与Fe@MWCNTs的[2+1]环加成反应既实现了有效的功能化又实现了药物“连接”。Fe@MWCNTs的亲水化对于有效的活性细胞摄取至关重要。尽管HMMs的暴露时间更长，但f-Fe@MWCNTs对T47D细胞的毒性比对HMMs大得多。最终，负载在β-环糊精笼中的5-氟尿嘧啶或与共价连接的紫红素的Fe@MWCNTs成为在磁场中最具细胞毒性且可操控的，有望成为mt-DDSs。
