Dual-Light-Primed GSH-Scavenging Lipid Hybrid Nanoplatform for Cascade-Activated Photodynamic Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Photodynamic Therapy

Background:

• Photodynamic therapy (PDT) faces challenges in tumor selectivity and drug delivery.
• Existing PDT methods struggle with inefficient activation and tumor antioxidant defenses.

Purpose of the Study:

• To develop a lipid-hybridized phototherapeutic nanoplatform (LBCIN) to overcome PDT limitations.
• To engineer a system with enhanced tumor selectivity, drug delivery, and synergistic therapeutic effects.

Main Methods:

• Designed a novel photosensitizer prodrug (BdTT-BNBE) activated by reactive oxygen species (ROS).
• Integrated a molecular logic gate for ROS-triggered activation and glutathione (GSH) scavenging.
• Encapsulated payload in a chondroitin sulfate core with a lipid corona for CD44-mediated targeting.
• Employed a dual-light strategy using 808 nm laser and white light-emitting diode (LED) irradiation.

Main Results:

• LBCIN demonstrated ROS-triggered activation, releasing an active photosensitizer and a pQM intermediate.
• The pQM intermediate scavenged GSH, dismantling the tumor's antioxidant defense.
• Dual-light irradiation enhanced nanoparticle uptake and induced potent PDT effects via energy transfer and ferroptosis.
• Achieved durable tumor eradication with a high safety profile.

Conclusions:

• LBCIN effectively integrates ROS-responsive chemistry and sequential light activation for enhanced PDT.
• The nanoplatform overcomes poor tumor selectivity and inefficient drug delivery challenges.
• This strategy offers a promising approach for durable tumor eradication with improved safety.