Ussia Martina, Urso Mario, Kratochvilova Monika, Navratil Jiri, Balvan Jan, Mayorga-Martinez Carmen C, Vyskocil Jan, Masarik Michal, Pumera Martin
Future Energy and Innovation Laboratory, Central European Institute of Technology, Brno University of Technology, Purkyňova 123, Brno, 61200, Czech Republic.
Department of Pathological Physiology, Faculty of Medicine, Masaryk University/Kamenice 5, Brno, CZ-625 00, Czech Republic.
Small. 2023 Apr;19(17):e2208259. doi: 10.1002/smll.202208259. Epub 2023 Jan 26.
Prostate cancer is the most commonly diagnosed tumor disease in men, and its treatment is still a big challenge in standard oncology therapy. Magnetically actuated microrobots represent the most promising technology in modern nanomedicine, offering the advantage of wireless guidance, effective cell penetration, and non-invasive actuation. Here, new biodegradable magnetically actuated zinc/cystine-based microrobots for in situ treatment of prostate cancer cells are reported. The microrobots are fabricated via metal-ion-mediated self-assembly of the amino acid cystine encapsulating superparamagnetic Fe O nanoparticles (NPs) during the synthesis, which allows their precise manipulation by a rotating magnetic field. Inside the cells, the typical enzymatic reducing environment favors the disassembly of the aminoacidic chemical structure due to the cleavage of cystine disulfide bonds and disruption of non-covalent interactions with the metal ions, as demonstrated by in vitro experiments with reduced nicotinamide adenine dinucleotide (NADH). In this way, the cystine microrobots served for site-specific delivery of Zn ions responsible for tumor cell killing via a "Trojan horse effect". This work presents a new concept of cell internalization exploiting robotic systems' self-degradation, proposing a step forward in non-invasive cancer therapy.
前列腺癌是男性中最常被诊断出的肿瘤疾病，其治疗在标准肿瘤治疗中仍然是一个巨大挑战。磁驱动微型机器人是现代纳米医学中最具前景的技术，具有无线引导、有效穿透细胞和非侵入性驱动的优势。在此，报道了一种用于原位治疗前列腺癌细胞的新型可生物降解的磁驱动锌/胱氨酸基微型机器人。这些微型机器人是在合成过程中通过金属离子介导的氨基酸胱氨酸对超顺磁性Fe₃O₄纳米颗粒（NPs）的自组装制备而成，这使得它们能够通过旋转磁场进行精确操控。在细胞内部，典型的酶促还原环境有利于氨基酸化学结构的分解，这是由于胱氨酸二硫键的断裂以及与金属离子非共价相互作用的破坏，用还原型烟酰胺腺嘌呤二核苷酸（NADH）进行的体外实验证明了这一点。通过这种方式，胱氨酸微型机器人通过“特洛伊木马效应”实现了负责杀死肿瘤细胞的锌离子的位点特异性递送所。这项工作提出了一种利用机器人系统自降解进行细胞内化的新概念，在非侵入性癌症治疗方面向前迈进了一步。
