We focused on the biomechanical and morphological characteristics of prostate cancer cells and their changes resulting from the effect of docetaxel, cisplatin, and long-term zinc supplementation. Cell population surviving the treatment was characterized as follows: cell stiffness was assessed by atomic force microscopy, cell motility and invasion capacity were determined by colony forming assay, wound healing assay, coherence-controlled holographic microscopy, and real-time cell analysis. Cells of metastatic origin exhibited lower height than cells derived from the primary tumour. Cell dry mass and CAV1 gene expression followed similar trends as cell stiffness. Docetaxel- and cisplatin-surviving cells had higher stiffness, and decreased motility and invasive potential as compared to non-treated cells. This effect was not observed in zinc(II)-treated cells. We presume that cell stiffness changes may represent an important overlooked effect of cisplatin-based anti-cancer drugs. Atomic force microscopy and confocal microscopy data images used in our study are available for download in the Zenodo repository (https://zenodo.org/, Digital Object Identifiers:10.5281/zenodo.1494935).

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 Fe3O4 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.

Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased aspartate/threonine, aspartate/methionine, and sarcosine/serine ratios were associated with cancer phenotype with high levels of sensitivity and specificity. Prostate 77: 604-616, 2017. © 2017 Wiley Periodicals, Inc.