A Comparison of Iron Oxide Particles and Silica Particles for Tracking Organ Recellularization.

Reseeding of decellularized organ scaffolds with a patient's own cells has promise for eliminating graft versus host disease. This study investigated whether ultrasound imaging or magnetic resonance imaging (MRI) can track the reseeding of murine liver scaffolds with silica-labeled or iron-labeled liver hepatocytes. Mesoporous silica particles were created using the Stöber method, loaded with Alexa Flour 647 fluorophore, and conjugated with protamine sulfate, glutamine, and glycine. Fluorescent iron oxide particles were obtained from a commercial source. Liver cells from donor mice were loaded with the silica particles or iron oxide particles. Donor livers were decellularized and reperfused with silica-labeled or iron-labeled cells. The reseeded livers were longitudinally analyzed with ultrasound imaging and MRI. Liver biopsies were imaged with confocal microscopy and scanning electron microscopy. Ultrasound imaging had a detection limit of 0.28 mg/mL, while MRI had a lower detection limit of 0.08 mg/mL based on particle weight. The silica-loaded cells proliferated at a slower rate compared to iron-loaded cells. Ultrasound imaging, MRI, and confocal microscopy underestimated cell numbers relative to scanning electron microscopy. Ultrasound imaging had the greatest underestimation due to coarse resolution compared to the other imaging modalities. Despite this underestimation, both ultrasound imaging and MRI successfully tracked the longitudinal recellularization of liver scaffolds.

Improved Treatment of Pancreatic Cancer With Drug Delivery Nanoparticles Loaded With a Novel AKT/PDK1 Inhibitor.

OBJECTIVES: This research study sought to improve the treatment of pancreatic cancer by improving the drug delivery of a promising AKT/PDK1 inhibitor, PHT-427, in poly(lactic-co-glycolic) acid (PLGA) nanoparticles. METHODS: PHT-427 was encapsulated in single-emulsion and double-emulsion PLGA nanoparticles (SE-PLGA-427 and DE-PLGA-427). The drug release rate was evaluated to assess the effect of the second PLGA layer of DE-PLGA-427. Ex vivo cryo-imaging and drug extraction from ex vivo organs was used to assess the whole-body biodistribution in an orthotopic model of MIA PaCa-2 pancreatic cancer. Anatomical magnetic resonance imaging (MRI) was used to noninvasively assess the effects of 4 weeks of nanoparticle drug treatment on tumor size, and diffusion-weighted MRI longitudinally assessed changes in tumor cellularity. RESULTS: DE-PLGA-427 showed delayed drug release and longer drug retention in the pancreas relative to SE-PLGA-427. Diffusion-weighted MRI indicated a consistent decrease in cellularity during drug treatment with both types of drug-loaded nanoparticles. Both SE- and DE-PLGA-427 showed a 6-fold and 4-fold reduction in tumor volume relative to untreated tumors and an elimination of primary pancreatic tumor in 68% of the mice. CONCLUSIONS: These results indicated that the PLGA nanoparticles improved drug delivery of PHT-427 to pancreatic tumors, which improved the treatment of MIA PaCa-2 pancreatic cancer.