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

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Photochemistry

Background:

• Controlled activation of platinum(IV) prodrugs for cancer therapy is challenging.
• Combining photodynamic therapy (PDT) and chemotherapy in a single molecule offers synergistic treatment potential.
• Existing methods often require specific reducing agents for drug release.

Purpose of the Study:

• To design and characterize a novel cisplatin-based platinum(IV) prodrug, Riboplatin.
• To investigate the dual-action capabilities of Riboplatin for photoactivated chemotherapy (PACT) and PDT.
• To demonstrate real-time, light-induced drug release and reactive oxygen species (ROS) generation within tumor spheroids.

Main Methods:

• Design and synthesis of a cisplatin-based Pt(IV) prodrug (Riboplatin) incorporating tetraacetylriboflavin.
• Utilizing an electrochemical sensor for real-time monitoring of prodrug behavior.
• Investigating light-induced activation within MCF-7 tumor spheroids.

Main Results:

• Riboplatin demonstrated dual-action capability, acting as both a PDT agent and a photoactivated chemotherapy agent.
• Gentle blue light irradiation triggered the release of cisplatin and generation of ROS without needing a reducing agent.
• Simultaneous photoactivated release of cisplatin and ROS was confirmed electrochemically inside living tumor spheroids.

Conclusions:

• Riboplatin represents a novel dual-action Pt(IV) prodrug for combined PACT and PDT.
• This study provides the first in-situ evidence of simultaneous photoactivated anticancer drug release and ROS generation from a single Pt(IV) prodrug within tumor spheroids.
• The findings highlight the potential of Riboplatin for targeted cancer therapy with enhanced efficacy and reduced side effects.