Co-delivery of Sorafenib and CRISPR/Cas9 Based on Targeted Core-Shell Hollow Mesoporous Organosilica Nanoparticles...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• CRISPR/Cas9 gene editing offers cancer treatment potential but faces safety and delivery challenges.
• Nonviral nanodelivery systems are crucial for safe and effective CRISPR/Cas9 applications in combination therapy.

Purpose of the Study:

• To develop a novel nonviral nanodelivery system for co-delivering CRISPR/Cas9 and sorafenib for cancer gene-chemo-combination therapy.
• To evaluate the safety, efficacy, and tumor inhibition of the developed nanocomplex in vitro and in vivo.

Main Methods:

• A polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle was constructed for co-delivery.
• The nanocomplex was assessed for drug loading, stability, targeted delivery, and controlled release.
• EGFR gene editing efficiency, off-target effects, and pathway regulation were analyzed.
• Tumor inhibition and in vivo safety were evaluated in a mouse model.

Main Results:

• The nanocomplex demonstrated high stability, drug loading, and controlled release capabilities.
• Achieved >60% EGFR gene editing efficiency without off-target effects, regulating the EGFR-PI3K-Akt pathway.
• Demonstrated synergistic effects on cell proliferation and 85% tumor inhibition in a mouse model.
• Showed high tumor accumulation in vivo with good safety and no damage to major organs.

Conclusions:

• The developed nanocomplex provides a versatile and safe delivery approach for gene-drug combinations.
• Precise gene editing and synergistic tumor growth inhibition were achieved without significant side effects.
• This nanodelivery system holds promise for efficient CRISPR/Cas9-based cancer gene therapy.