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首页> 美国卫生研究院文献>Journal of Visualized Experiments : JoVE >Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance
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Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

机译：定制设计的基于激光的加热设备用于在磁共振图像引导下从热敏脂质体中触发顺铂释放

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Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e., gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.
机译：脂质体已被用作药物递送系统，通过利用增强的通透性和保留（EPR）效应来靶向实体瘤，从而导致全身毒性的显着降低。然而，从脂质体释放的包封药物不足限制了它们的临床功效。为了克服有限的肿瘤药物生物利用度的问题，已经对温度敏感性脂质体进行了工程设计以提供药物的部位特异性释放。我们的实验室设计并开发了一种热活化的顺铂热敏脂质体制剂（CDDP），称为HTLC，可在实体瘤上触发CDDP的释放。使用定制的基于激光的加热设备在鼠模型中实现了体内热激活递送，该加热设备可通过MR测温（MRT）确认在肿瘤部位提供保形加热模式。使用光纤温度监控设备实时测量整个加热期间的温度，并通过交替改变激光功率在线调节热量的传递。在磁共振（MR）图像引导下，通过将MR造影剂（即加多利多）与CDDP共封装到热敏脂质体中来优化药物输送，以此作为验证加热方案和评估肿瘤蓄积的手段。加热方案包括在给予HTLC之前5分钟的预热时间和注射后20分钟的加热时间。与未加热的肿瘤和肌肉相比，该加热方案导致被包封的药剂的有效释放具有在加热的肿瘤中观察到的最高MR信号变化。这项研究证明了基于激光的加热设备在临床前热敏脂质体开发中的成功应用，以及MR引导的加热方案验证对优化药物输送的重要性。

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