In Vitro/In VivoElectrochemical Detection of Pt(II) Species

Abstract

The biodistribution of chemotherapy compounds within tumor tissue is one of the main challenges in the development of antineoplastic drugs, and techniques for simple, inexpensive, sensitive, and selective detection of various analytes in tumors are of great importance. In this paper we propose the use of platinized carbon nanoelectrodes (PtNEs) for the electrochemical detection of platinum-based drugs in various biological models, including single cells and tumor spheroids in vitro and inside solid tumors in vivo. We have demonstrated the quantitative direct detection of Pt(II) in breast adenocarcinoma MCF-7 cells treated with cisplatin and a cisplatin-based DNP prodrug. To realize the potential of this technique in advanced tumor models, we measured Pt(II) in 3D tumor spheroids in vitro and in tumor-bearing mice in vivo. The concentration gradient of Pt(II) species correlated with the distance from the sample surface in MCF-7 tumor spheroids. We then performed the detection of Pt(II) species in tumor-bearing mice treated intravenously with cisplatin and DNP. We found that there was deeper penetration of DNP in comparison to cisplatin. This research demonstrates a minimally invasive, real-time electrochemical technique for the study of platinum-based drugs.

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

“…We reasonably assume that the Pt­(IV) prodrugs designed would release cisplatin in the intracellular environment. Having previously succeeded in the electrochemical detection of cisplatin in cells, in spheroids, and in vivo, in this work, we evaluated the penetrating ability of Pt­(IV) prodrugs using the same approach.…”

“…Until now, the use of electrochemical techniques for platinum-based drug detection was limited to buffer solutions and biological fluids. − Recently, we have reported the first example of electrochemical detection of Pt 2+ species in biological objects using a 60 nm Pt-coated carbon nanoelectrode (PtNE). The ability of the PtNE-based technique to quantify Pt 2+ species in single cells, 3D tumor spheroids, and tumors in vivo was proved …”

“…The key task of the study was the development of a cisplatin-based Pt­(IV) prodrug capable of delivering a greater amount of cisplatin in the tumor as compared with the administration of the same dose of cisplatin or the previously reported DNP prodrug. To study the accumulation of cisplatin in a tumor in vivo, we applied the latest method of intravital postinjection electrochemical detection of cisplatin in tumors using a Pt-coated nanoelectrode …”

Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area

“…Electrochemical detection of Pt 2+ species in biological objects based on a platinized nanoelectrode allows one to quantify the amount of platinum-based drugs directly inside a therapeutic target and thus evaluate the drug efficacy. Having previously succeeded in the electrochemical detection of cisplatin in cells, spheroids, and in vivo, , in this work, we evaluate a hypoxia-induced metabolism of the Pt-Mnz prodrug using the same approach. The three-dimensional (3D) spheroid proved to be a useful tool for studying hypoxia and hypoxia-activated agents given those cellular cultures are relatively close models of real tumors. − …”

“…Nanopipette is a unique platform in single-cell chemistry. − Carbon nanoelectrodes (CNEs) are actively used for the measurement of reactive oxygen and nitrogen species (ROS/RNS) in single cells. − We had also previously detected ROS electrochemically at the single cell level − and in vivo using Pt-coated CNEs (PtNEs). Recently, we had developed a PtNE-based technique able to quantify Pt­(II) species in individual cells, cellular spheroids, tumors, and tissues in vivo . More recently, we used the PtNE-based technique to evaluate the efficacy of various Pt­(IV) prodrugs in a spheroid tumor model and in vivo …”