Thermosensitive liposomes: a promising step toward localised chemotherapy

Many small molecules and biologic therapeutics have been developed for solid tumor therapy. However, the unique physiology of tumors makes the actual delivery of these drugs into the tumor mass inefficient. Such delivery requires transport from blood vessels, across the vasculature and into and through interstitial space within a tumor. This transportation is dependent on the physiochemical properties of the therapeutic agent and the biological properties of the tumor. It was hoped the application of nanoscale drug carrier systems would solve this problem. However, issues with poor tumor accumulation and limited drug release have impeded clinical impact. In response, these carrier systems have been redesigned to be paired with targetable external mechanical stimuli which can trigger much enhanced drug release and deposition. The pre-clinical and clinical progress of thermolabile drug carrier systems and the modalities used to trigger the release of their cargo are assessed. Combined application of mild hyperthermia and heat-responsive liposomal drug carriers has great potential utility. Clinical trials continue to progress this approach and serve to refine the technologies, dosing regimens and exposure parameters that will provide optimal patient benefit.

针对实体瘤（solid tumor）治疗，已开发出诸多小分子药物与生物治疗剂。然而，肿瘤独特的生理学特性导致这类药物实际递送至肿瘤实体的效率极低。这类药物递送需先从血管出发，穿过脉管系统（vasculature），进入并穿透肿瘤内部的间质间隙。该转运过程取决于治疗剂的理化性质与肿瘤的生物学特性。此前人们曾期望，纳米级药物载体系统（nanoscale drug carrier systems）的应用可解决这一难题。然而，肿瘤蓄积不足与药物释放受限等问题，仍制约了其临床应用价值。为此，研究人员对这类载体系统进行了重新设计，使其可与可靶向的外部机械刺激联用，从而大幅增强药物释放与沉积效果。本文评估了热敏型药物载体系统（thermolabile drug carrier systems）的临床前与临床研究进展，以及用于触发其载荷释放的各类手段。温和热疗（mild hyperthermia）与热响应脂质体药物载体的联合应用，展现出极佳的应用潜力。相关临床试验正持续推进该疗法的发展，并不断优化相关技术、给药方案与暴露参数，以期为患者带来最优获益。