Case Western Reserve University,
Keywords: cancer, drug delivery, nanobubble, nanomedicine
Summary:Drug delivery for cancer therapy remains challenging despite the immense promise of nanomedicine. To meet the urgent need for more effective treatment options, we are developing a hybrid polymer-lipid theranostic nanoparticles (called nanobubbles) which are inherently ultrasound visible and ultrasound-deployable on demand in real-time at the region of interest. Preliminary data demonstrate that even after a single application of ultrasound immediately following particle injection, ultrasound-enhanced delivery leads to significantly higher drug concentration in tumors, and results in more homogeneous distribution within tumor and individual tumor cells compared to free drug and non-triggered particles. This suggests that, especially after parameters are optimized, treatment of tumors with the nanobubble has the potential to maximize drug dose at the tumor site and should lead to improved survival. Some aspects that distinguish our technology from others include 1) nanoparticles used in the study are 100-200 nm in diameter which are echogenic at clinically relevant frequencies of 3-12 MHz; 2) nanoparticles have augmented cargo capacity to enable simple and efficient drug loading directly into the particle; 3) payload release can be triggered with the imaging transducer using standard pulse sequences already available on clinical scanners; 4) nanoparticle is self-assembled and thus easily formulated and scaled up. The ultimate goal of this work is to develop and optimize an image-guided drug delivery strategy that will maximize drug accumulation in tumors and lead to augmented, homogeneous drug distribution within the tumor volume while minimizing systemic accumulation compared to free drug. The outcome of this research will be a more effective strategy to improve delivery of chemotherapeutic agents to primary and metastatic tumors. Current applications under investigation include delivery to liver metastasis from colorectal cancer and metastatic liver cancer.