Liposomal form of 2-alkylthioimidazolone-based copper complexes for combined cancer therapy.

Aim: To develop an optimized approach for encapsulating a 2-alkylthioimidazolone-based copper coordination compound within liposomes, which could offer treatment of cancer and bacterial infections by reactive oxygen species generation toxicity mechanisms. Materials & methods: For drug-loaded liposome preparation, lipids and drug mixture in organic solvents was injected into copper salt solution, forming a coordination compound simultaneously embedded in the lipid bilayer. In vitro tests were performed on MCF7 and MDA-MB-231 breast cancer cells. Results: Liposomes had a loading capacity of up to 1.75% (molar drug-to-lipid ratio). In vitro tests showed increased viability and accumulation of the liposomal formulation compared with free drug as well as lack of cytotoxicity in hepatocytes. Conclusion: This optimized technique for encapsulating large copper complexes in liposomes could be used to improve their delivery and better treat cancer and bacterial infections.

This work introduces a new technique for copper-containing drugs encapsulation in a drug-delivery system. The drug, a promising copper compound, is embedded in lipid nanovesicles ­ tiny fat particles ­ for intravenous injection. In addition to chemical characterization of the obtained drug form, tests on cancer cells showed a noticeable effect, whereas healthy cell types were not harmed. Copper possesses not only anticancer effects but also antimicrobial properties, which are also shown by the drug form, and a test of combined suppression of cancer cell lines and bacteria was successful. Hence, the obtained drug form has the potential for dual treatment of cancer and bacterial infections.

Photoinduced Reduction of Novel Dual-Action Riboplatin Pt(IV) Prodrug.

Controlled photoreduction of Pt(IV) prodrugs is a challenging task due to the possibility of targeted light-controlled activation of anticancer agents without affecting healthy tissues. Also, a conjugation of photosensitizers and clinically used platinum drugs into one Pt(IV) prodrug allows combining photodynamic therapy and chemotherapy approaches into one molecule. Herein, we designed the cisplatin-based Pt(IV) prodrug Riboplatin with tetraacetylriboflavin in the axial position. A novel Pt(IV) prodrug is able to act both as a photodynamic therapy (PDT) agent through the conversion of ground-state 3O2 to excited-state 1O2 and as an agent of photoactivated chemotherapy (PACT) through releasing of cisplatin under gentle blue light irradiation, without the requirement of a reducing agent. The light-induced behavior of Riboplatin was investigated using an electrochemical sensor in MCF-7 tumor spheroids. Photocontrolled cisplatin release and ROS generation were detected electrochemically in real time. This appears to be the first confirmation of simultaneous photoactivated release of anticancer drug cisplatin and ROS from a dual-action Pt(IV) prodrug observed from the inside of living tumor spheroids.