Light-Responsive Pt(IV) Prodrugs with Controlled Photoactivation and Low Dark Toxicity.

Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.

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.

Therapeutic Potential of Hispidin-Fungal and Plant Polyketide.

There is a large number of bioactive polyketides well-known for their anticancer, antibiotic, cholesterol-lowering, and other therapeutic functions, and hispidin is among them. It is a highly abundant secondary plant and fungal metabolite, which is investigated in research devoted to cancer, metabolic syndrome, cardiovascular, neurodegenerative, and viral diseases. This review summarizes over 20 years of hispidin studies of its antioxidant, anti-inflammatory, anti-apoptotic, antiviral, and anti-cancer cell activity.