Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, Pizzale Aldo Moro 5, 00185, Rome, Italy.
Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology and Medical Embryology, Sapienza University of Rome, laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Via A. Scarpa, 14-16, 00161, Rome, Italy.
Sci Rep. 2019 Aug 13;9(1):11749. doi: 10.1038/s41598-019-48037-z.
In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the "heavy duty" carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells.
在这项工作中，我们利用嵌合古菌-人铁蛋白的独特性质，将细胞色素 c 包裹、递送至髓性白血病细胞系并使其释放，从而诱导细胞凋亡。该嵌合蛋白结合了古菌铁蛋白 24 聚体组装的多功能性和货物掺入能力，以及人 H 铁蛋白与 CD71 的特异性结合，CD71 是负责转铁蛋白-铁摄取的“重载”载体。通过体外实验，成功地将铁蛋白包裹的细胞色素 C 递送至急性早幼粒细胞白血病（APL）NB4 细胞系，该细胞系对传统转染方法具有很强的抗性。通过双荧光标记证明，细胞色素 C 在细胞溶质环境中的有效释放诱导了癌细胞凋亡。
