Acoustically Driven Hybrid Nanocrystals for In Vivo Pancreatic Cancer Treatment.

Summary

Lipid-coated, iron-doped ZnO nanoparticles loaded with a fluorescent sonosensitizer induced ROS and cytotoxicity in KPC PDAC cells and, when delivered intratumorally and activated by ultrasound, increased immune infiltration, apoptosis, and survival in a murine subcutaneous PDAC model. AlexaFluor 700 labeling enabled in situ tracking while minimizing off-target exposure.

Key Findings

• Sonosensitizer-loaded, lipid-coated iron-doped ZnO nanoparticles plus ultrasound induced significant ROS and reduced KPC PDAC cell viability in vitro.
• Intratumoral delivery with ultrasound produced synergistic antitumor effects in vivo, increasing immune cell infiltration and apoptosis.
• Treatment prolonged survival in a subcutaneous murine PDAC model and allowed in situ nanoparticle tracking via AlexaFluor 700.

Clinical Implications

While preclinical, this platform suggests a non-thermal, imageable local adjunct that could complement surgery/chemotherapy and potentially convert PDAC to a more immunoresponsive state.

Limitations

• Subcutaneous PDAC model rather than orthotopic disease may not recapitulate stromal barriers and perfusion of native pancreas
• Intratumoral administration limits generalizability to systemic delivery scenarios
• Long-term toxicity, clearance, and off-target safety profiles were not reported

Future Directions

Validate in orthotopic and immunocompetent PDAC models, optimize ultrasound parameters/dosing, characterize pharmacokinetics and toxicity in large animals, and test combinations with chemotherapy and immunotherapy.