Development of an ultrasound-mediated nano-sized drug-delivery system for cancer treatment: from theory to experiment

Aim: To establish a methodology for understanding how ultrasound (US) induces drug release from nano-sized drug-delivery systems (NSDDSs) and enhances drug penetration and uptake in tumors. This aims to advance cancer treatment strategies.
Materials & methods: We developed a multi-physics mathematical model to elucidate and understand the intricate mechanisms governing drug release, transport and delivery. Unique in vitro models (monolayer, multilayer, spheroid) and a tailored US exposure setup were introduced to evaluate drug penetration and uptake.
Results: The results highlight the potential advantages of US-mediated NSDDSs over conventional NSDDSs and chemotherapy, notably in enhancing drug release and inducing cell death.
Conclusion: Our sophisticated numerical and experimental methods aid in determining and quantifying drug penetration and uptake into solid tumors.
Therapeutic ultrasound (TUS) permits targeted drug delivery by controlling the drug-release kinetics, thereby enhancing drug delivery and cell killing in tumors.
Our study enabled a comprehensive understanding of the integration of TUS and nano-sized drug-delivery systems by combining experimental and theoretical analyses.
We introduced a multi-scale and multi-physics mathematical and computational model for the penetration of TUS-triggered nano-sized drug-delivery systems into solid tumors.
We examined three in vitro cancer cell culture methods – 2D monolayer, 3D spheroids and 3D multi-layer cells – to analyze initial cell toxicity, antiproliferative capacity and drug penetration.
A customized experimental setup was developed that was suitable for TUS (i.e., LIPUS) and cell studies.
The synergies between TUS, drug-release kinetics and transport characteristics were explored to increase the rate of cancer cell death.
We proposed an optical sectioning technique for drug-penetration studies and utilized flow cytometry analysis for cell proliferation studies in a spheroid cancer cell model.
Drug-release kinetics were determined with and without ultrasound exposure at 37°C.