Ultrasound‐Triggered Delivery of Iproplatin from Microbubble‐Conjugated Liposomes

The PtIV prodrug iproplatin has been actively loaded into liposomes using a calcium acetate gradient, achieving a 3‐fold enhancement in drug concentration compared to passive loading strategies. A strain‐promoted cycloaddition reaction (azide‐ dibenzocyclooctyne) was used to attach iproplatin‐loaded liposomes L(Pt) to gas‐filled microbubbles (M), forming an ultrasound‐responsive drug delivery vehicle [M−L(Pt)]. Ultrasound‐triggered release of iproplatin from the microbubble‐liposome construct was evaluated in cellulo. Breast cancer (MCF‐7) cells treated with both free iproplatin and iproplatin‐loaded liposome−microbubbles [M−L(Pt)] demonstrated an increase in platinum concentration when exposed to ultrasound. No appreciable platinum uptake was observed in MCF‐7 cells following treatment with L(Pt) only or L(Pt)+ultrasound, suggesting that microbubble‐mediated ultrasonic release of platinum‐based drugs from liposomal carriers enables greater control over drug delivery.
Actively loading platinum(IV) prodrug iproplatin into liposomes has been achieved using a calcium acetate gradient. Microbubble‐mediated release and accumulation of the prodrug in MCF7 cancer cells following ultrasound treatment demonstrates that this strategy can enable greater control over drug delivery.