Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States.
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, United States.
Adv Cancer Res. 2018;139:121-146. doi: 10.1016/bs.acr.2018.04.004.
Liposomes have been employed as cancer therapy clinically since the 1990s, with the primary benefit of reduced toxicity but no appreciable efficacy improvement. Thermosensitive liposomes (TSLs) are specifically formulated such that they release the encapsulated drug when exposed to hyperthermic temperatures in the fever range (~40-42°C) and have been investigated as cancer therapy for several decades, with first clinical trials initiated in the last decade. Combined with localized hyperthermia, TSLs allow precise drug delivery to a targeted region. Typically, the targeted tissue is exposed to localized hyperthermia facilitated by an image-guided hyperthermia device. Thus, TSLs enable image-guided drug delivery where drug is delivered to a tissue region identified by medical imaging. Recent TSL formulations are based on the more recent paradigm of intravascular triggered release, where drug is released rapidly (within seconds) while TSLs pass through the vasculature of the heated tissue region. The drug released within the blood then extravasates and is taken up by cancer cells. These TSLs enable up to 20-30 times higher tumor drug uptake compared to infusion of unencapsulated drug, and the dose locally delivered to the heated region can be modulated based on heating duration. This chapter reviews various TSL formulations, the different anticancer agents that have been encapsulated, as well as targeted cancer types. Further, the various hyperthermia devices that have been used for image-guided hyperthermia are reviewed, focusing on those that have been employed in human patients.
自 20 世纪 90 年代以来，脂质体已被临床用于癌症治疗，其主要优势在于降低毒性，但疗效并无明显改善。热敏脂质体（TSL）是专门设计的，当暴露于发热范围内的高温（约 40-42°C）时，它们会释放包裹的药物，并已被研究用于癌症治疗数十年，最初的临床试验是在过去十年中启动的。与局部热疗相结合，TSL 可以精确地将药物递送到靶向区域。通常，目标组织会暴露在由图像引导的热疗设备辅助的局部热疗中。因此，TSL 能够实现图像引导的药物输送，即将药物输送到通过医学成像识别的组织区域。最近的 TSL 制剂基于最近的血管内触发释放范式，其中药物在 TSL 通过加热组织区域的血管时迅速释放（在几秒钟内）。然后，释放到血液中的药物渗出并被癌细胞吸收。与输注未包裹的药物相比，这些 TSL 使肿瘤的药物摄取量增加了 20-30 倍，并且可以根据加热持续时间来调节递送到加热区域的局部剂量。本章回顾了各种 TSL 制剂、已封装的不同抗癌药物以及靶向癌症类型。此外，还回顾了用于图像引导热疗的各种热疗设备，重点介绍了那些已在人类患者中使用的设备。
