[论文解读] Delivery of Liquid Metal to the Target Vessels as Vascular Embolic Agent to Starve Diseased Tissues or Tumors to Death

Qian Wang, Yang Yu+1 more|arXiv (Cornell University)|Aug 4, 2014

Sarcoma Diagnosis and Treatment参考文献 27被引用 9

一句话总结

本研究提出将液态金属作为一种新型血管栓塞剂用于肿瘤饥饿疗法，利用其在体温下液固相变的独特特性，实现对肿瘤供血血管的完全且稳定的闭塞。在兔和小鼠中的活体实验证实了有效的栓塞及组织破坏，其CT可见性支持诊断与治疗一体化，展现出作为传统栓塞剂的有前途的替代方案。

ABSTRACT

Tumor growth relies heavily on the continuous blood and nutrients supply. Theoretically, it is an ideal therapeutic way of killing tumor by only vascular embolization. However, most of the existing vascular embolic agents are still rather insufficient to fulfill the real clinical need due to the reasons like: incomplete filling of target vasculature, being easily washed away by blood or body solution, or just producing toxicity to tissues. Here from an alternative way, the body temperature liquid metal, a kind of soft and highly compliant material, was proposed for the first time as blood vessel embolization agent for tumor physical therapy. With its unique capability of easy phase transition between liquid and solid state and sub-cooling behavior, such material can be fluently injected into the tiny vessels including ending capillaries and fully block them. The in vitro cytotoxicity experiments were performed which showed that treating localized diseased tissues through liquid metal embolic agent is acceptable. Endowed with a high density, the liquid metal-filled vessels are highly visible under the CT scan, which offers the potential of diagnosis-treatment integration. To further demonstrate the new conceptual liquid metal vascular embolization therapy, several experiments on in vivo vasculatures of rabbit ears and mouse tails were performed to provide evidences of destroying the targeted tissues. To interpret the liquid metal starvation therapy effects, a theoretical model was established to simulate the tumor growth with zero, partial or complete filling of the metal agent inside the vessels. All the results support that, given appropriate administration, the liquid metal embolization is able to destruct the target regions and might starve the tumors to death through a relatively easy way. This study lays the foundation of a promising tumor starvation therapy in the coming time.

研究动机与目标

• 为解决现有栓塞剂的临床局限性，如血管填充不完全、洗脱现象及毒性问题。
• 探索一种利用在体温下可在液态与固态之间转变的材料，实现新型物理机制的肿瘤栓塞。
• 评估液态金属作为兼具诊断与治疗功能的双用途栓塞剂的可行性与安全性。
• 证明液态金属栓塞在破坏靶组织血供方面的活体疗效。
• 建立理论模型，模拟不同程度血管闭塞下肿瘤的生长动力学。

提出的方法

• 采用一种在体温下具有过冷行为的液态金属（如伽罗宁）以实现其在液态下易于注射，并在血管内稳定固化。
• 进行体外细胞毒性试验，评估液态金属对局部组织的生物相容性。
• 在兔耳和小鼠尾部血管系统中开展活体实验，评估栓塞成功率及组织破坏程度。
• 采用CT扫描可视化高密度液态金属填充的血管，实现实时影像引导。
• 建立理论数学模型，模拟在完全、部分或零血管闭塞条件下肿瘤的生长。
• 分析液态金属在微血管内注射及固化过程中的力学与血流动力学行为。

实验结果

研究问题

• RQ1 液态金属能否有效输送并保留在细小的终末毛细血管中，以实现完全的血管闭塞？
• RQ2 该液态金属栓塞剂是否能诱导足够的细胞毒性以破坏肿瘤组织，且无全身毒性？
• RQ3 液态金属的高CT可见性在多大程度上支持诊断与治疗的一体化？
• RQ4 血管闭塞程度（完全 vs. 部分）在理论模型中如何影响肿瘤的生长动力学？
• RQ5 液态金属的相变行为是否能实现可靠的栓塞，而不会导致血管破裂或栓塞？

主要发现

• 体外细胞毒性试验证实，该液态金属栓塞剂具有生物相容性，适用于局部组织治疗。
• 活体实验显示，兔耳和小鼠尾部微血管成功实现栓塞，观察到完全的血管闭塞。
• 液态金属填充的血管在CT下高度可见，支持实时影像引导，并具备图像融合治疗的潜力。
• 理论模型预测，完全血管闭塞可显著抑制肿瘤生长，支持饥饿疗法机制。
• 液态金属在体温下由液态转变为固态的能力，实现了稳定且持久的闭塞，无洗脱现象。
• 本研究为液态金属作为具有诊断与治疗潜力的有前途的多功能栓塞剂提供了概念验证。