Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5–15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm³). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.

溶血热敏脂质体 (LTSL) 专门设计用于在轻度高热条件下释放化疗药物。临床前研究表明，磁共振 (MR) 引导的聚焦超声 (FUS) 系统可以使用实时测温产生控制良好的体积热疗。然而，这些药物递送方法的高通量临床转化具有挑战性，尤其是因为 MR 引导的巨大成本开销和需要临床加热的更大体积。在非灌注离体中使用带有热敏电阻的超声引导体外临床 FUS 设备（重庆海富，JC200）在带有肋骨的牛肝组织模型中，我们提出了一种优化策略，用于在大组织体积 (≤92 cm ³ ) 中快速诱导 (5-15 分钟) 和维持 (>30 分钟) 轻度高热 (Δ T <+4°C )。我们描述了 LTSL 靶向药物递送的首次人体临床试验中的成功临床转化（TARDOX：一项研究肝肿瘤中热敏脂质体药物释放的 I 期研究），其中靶向肿瘤热疗导致局部化学消融. 加热策略可能适用于其他适应症和超声引导的 FUS 设备。