Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ, UK.
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
ChemistryOpen. 2021 Dec;10(12):1170-1176. doi: 10.1002/open.202100222. Epub 2021 Oct 27.
The Pt 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.
Pt 前药异丙铂已通过醋酸钙梯度积极载入脂质体，与被动载药策略相比，药物浓度提高了 3 倍。利用应变促进的环加成反应（叠氮化物-二苯并环辛炔）将载有异丙铂的脂质体 L(Pt) 连接到充有气体的微泡 (M) 上，形成超声响应性药物递送载体 [M-L(Pt)]。在细胞内评估了微泡-脂质体构建体中异铂的超声触发释放。用游离异铂和载有异铂的脂质体-微泡 [M-L(Pt)] 处理的乳腺癌 (MCF-7) 细胞在暴露于超声时显示铂浓度增加。仅用 L(Pt) 或 L(Pt)+超声处理 MCF-7 细胞后，未观察到明显的铂摄取，这表明从脂质体载体中通过微泡介导的超声释放铂类药物能够更好地控制药物递送。
