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 Fe3 O4 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 Zn2+ 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.

BIOCEV 1st Faculty of Medicine Charles University Průmyslová 595 25250 Vestec Czech Republic

Center for Advanced Functional Nanorobots Department of Inorganic Chemistry Faculty of Chemical Technology University of Chemistry and Technology Prague Technická 5 Prague 16628 Czech Republic

Department of Chemical and Biomolecular Engineering Yonsei University 50 Yonsei ro Seodaemun gu Seoul 03722 Republic of Korea

Department of Medical Research China Medical University Hospital China Medical University No 91 Hsueh Shih Road Taichung 40402 Taiwan

Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Faculty of Electrical Engineering and Computer Science VSB Technical University of Ostrava 17 listopadu 2172 15 Ostrava 70800 Czech Republic

Future Energy and Innovation Laboratory Central European Institute of Technology Brno University of Technology Purkyňova 123 Brno 61200 Czech Republic

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$a 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 Fe3 O4 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 Zn2+ 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.

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