Functionalized Photoimmune Hydrogel Microspheres for Inside-Out Eradication of Osteosarcoma via a PD-L1 PROTAC...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Osteosarcoma immunotherapy is hindered by the immunosuppressive tumor microenvironment.
• Targeting PD-L1 is a key strategy to enhance anti-tumor immunity.

Purpose of the Study:

• To develop a novel immunogel microsphere (CP-MOF@gel) for precise PD-L1 protein degradation in osteosarcoma.
• To investigate the efficacy of CP-MOF@gel in reversing the immunosuppressive tumor microenvironment and enhancing immunotherapy.

Main Methods:

• Core-shell nanoparticles encapsulating Cypate and a PROTAC PD-L1 degrader (ppd) were synthesized.
• Microfluidic and photocuring techniques were used to create CP-MOF@gel.
• In vitro and in vivo studies assessed the system's drug release, ROS generation, photothermal effects, pyroptosis induction, and anti-tumor immunity.

Main Results:

• CP-MOF@gel demonstrated optimized synthesis for enhanced drug loading and reduced particle size.
• The system effectively released CP-MOFs, triggered pyroptosis, and induced photothermal effects upon irradiation.
• CP-MOF@gel significantly enhanced T-cell-mediated killing and improved immunotherapy outcomes in vivo.

Conclusions:

• CP-MOF@gel provides a precision PROTAC-based protein degradation strategy for osteosarcoma suppression.
• This 'inside-out' therapeutic approach effectively reverses the immunosuppressive tumor microenvironment.