Orthogonal upconversion nanocarriers for combined photodynamic therapy and precisely triggered gene silencing in combating keloids.

Summary

This preclinical study engineers orthogonal upconversion nanocarriers to co-deliver siBACH1 and enable NIR-triggered photodynamic therapy, achieving spatiotemporal control in keloid fibroblasts. The platform induces apoptosis, suppresses proliferation, and reduces M2 macrophage recruitment via Rap1/MEK/ERK modulation.

Key Findings

• Designed OUNCs combining UCNPs, Rose Bengal, ROS-sensitive SeSe linkers, siBACH1, and HA for KF targeting.
• Achieved spatiotemporal siBACH1 release with NIR-triggered PDT, inducing KF apoptosis and inhibiting proliferation.
• Reduced M2 macrophage recruitment and modulated Rap1/MEK/ERK signaling in keloid models.

Clinical Implications

While not yet ready for clinical use, the approach suggests a future pathway for localized, light-triggered, targeted keloid therapies that could reduce recurrence and minimize systemic exposure.

Limitations

• Preclinical study without human clinical data; in vivo efficacy and safety remain to be established.
• Potential phototoxicity, biodistribution, and long-term nanoparticle safety not addressed.

Future Directions

Evaluate in vivo biodistribution, toxicity, dosing windows, and efficacy in animal models; optimize light dosing and carrier composition; progress to first-in-human feasibility studies.