Dual-drug loaded ultrasound-responsive nanodroplets for on-demand combination chemotherapy

Phase-changing nanodroplets are nanometric sized constructs that can be vaporized via external stimuli, such as focused ultrasound, to generate gaseous bubbles that are visible in ultrasound. Their activation can also be leveraged to release their payload, creating a method for ultrasound-modulated localized drug delivery. Here, we develop a perfluoropentane core nanodroplet that can simultaneously load paclitaxel and doxorubicin, and release them in response to an acoustic trigger. A double emulsion method is used to incorporate the two drugs with different physio-chemical properties, which allows for a combinatorial chemotherapy regimen to be used. Their loading, release, and biological effects on a triple negative breast cancer mouse model are investigated. We show that activation enhances the drug-delivery effect and delays the tumor growth rate in vivo. Overall, the phase-changing nanodroplets are a useful platform to allow on-demand delivery of combinations of drugs.

Automated summary

Phase-changing nanodroplets are nanometric sized constructs that can be vaporized via external stimuli to generate visible bubbles in ultrasound. Our study develops a perfluoropentane core nanodroplet that can load and release paclitaxel and doxorubicin in response to an acoustic trigger. We investigate their loading, release, and biological effects on a breast cancer mouse model, showing enhanced drug-delivery effect and delayed tumor growth rate. Overall, phase-changing nanodroplets are a useful platform for on-demand delivery of drug combinations.