A light-driven dual-nanotransformer with deep tumor penetration for efficient chemo-immunotherapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Designing transformable nanosystems for improved tumor accumulation and penetration is challenging.
• Tuning physicochemical properties of nanomedicine is crucial for effective cancer therapy.

Purpose of the Study:

• To develop a near-infrared (NIR) light-driven nanosystem with dual-transformation capabilities for enhanced tumor penetration.
• To create a nanomedicine that combines chemotherapy with chemo-immunotherapy for improved breast cancer treatment.

Main Methods:

• A core-shell nanotransformer was engineered using ROS-responsive silica nanoparticles and a thermosensitive ICG-hybrid shell.
• Doxorubicin (DOX) was loaded into the nanotransformer, which exhibited negative charge for prolonged circulation and tumor accumulation.
• NIR light irradiation triggered photothermal effects and ROS generation, leading to shell dissociation and core degradation.

Main Results:

• The nanotransformer underwent negative-to-positive charge reversal and matrix degradation upon NIR irradiation, producing smaller DOX-containing fragments.
• This dual transformation facilitated deep tumor penetration and effective chemotherapy, inducing immunogenic cell death in vitro and in vivo.
• Combined with PD-1 blockade, the nanotransformer significantly inhibited primary tumor growth and metastasis with low toxicity.

Conclusions:

• The developed light-transformable nanomedicine offers a promising strategy for high tumor accumulation and deep penetration.
• This approach enables efficient and safe chemo-immunotherapy for breast cancer, demonstrating significant therapeutic potential.