Liu Jing, Deng Zhong-Shan
Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
J Nanosci Nanotechnol. 2009 Aug;9(8):4521-42. doi: 10.1166/jnn.2009.1264.
In clinics, the minimally invasive freezing therapy, commonly known as cryosurgery, has been increasingly used for the controlled destruction of tumor tissue. However, there are still many bottlenecks to impede the success of a cryosurgery. One of the most critical factors has been that insufficient or inappropriate freezing will not completely destroy the target tumor tissues, which as a result may lead to tumor regenesis and thus failure of treatment. In addition, the surrounding healthy tissues may suffer from serious freeze injury due to unavoidable release of a large amount of cold from the freezing probe. To resolve these challenges, we recently proposed a new strategy, termed as nano-cryosurgery, to improve freezing efficiency of the conventional cryosurgical procedure. The basic principle of this protocol is to deliver functional suspension of nanoparticles with favorable physical and/or chemical properties into the target tissues, which then serve as adjuvant or drug carrier either to maximize the freezing heat transfer process, regulate freezing scale, modify ice-ball formation orientation or prevent the surrounding healthy tissues from being frozen. In addition, introduction of nanoparticles during cryosurgery could also help better image the edge of a tumor as well as the margin of the iceball. The new therapy raised many critical fundamental as well as practical issues for solving. This review is dedicated to present a comprehensive review on multiscale fundamental phase change heat transfer issues thus involved. Attentions would span from micro-scale heat transfer in cellular scale to tissue level. Some related thermal physical effects of nanoparticles on the freezing process such as ice nucleation enhancement, water transport during freezing of a single cell will be discussed. Cryosurgical thermal management of using nanoparticles to modify thermal properties of the tissue-particle components, regulate the growth orientation and strength of an ice ball, enable a conformal tumor destruction in tissues with or without large blood vessels, etc. will be illustrated. Meanwhile, the fundamental issue for the transport of nanoparticle and its assisted drug delivery will be summarized. Theoretical modeling as well as experimental approaches for studying the micro/nano-scale heat transfer throughout the tissue or cell domain during nano-cryosurgery will be suggested. Some potential applications and possible challenges when nanotechnology meets cryosurgery will be outlined. The nano-cryosurgery is expected to help expand the boundary of the emerging frontier of nano-biomedical engineering.
在临床上，微创冷冻疗法，通常称为冷冻手术，已越来越多地用于可控地破坏肿瘤组织。然而，仍有许多瓶颈阻碍冷冻手术的成功。最关键的因素之一是冷冻不足或不适当不会完全破坏目标肿瘤组织，结果可能导致肿瘤再生，从而导致治疗失败。此外，由于冷冻探针不可避免地释放大量冷量，周围的健康组织可能会遭受严重的冷冻损伤。为了解决这些挑战，我们最近提出了一种新策略，称为纳米冷冻手术，以提高传统冷冻手术的冷冻效率。该方案的基本原理是将具有良好物理和/或化学性质的纳米颗粒功能悬浮液输送到目标组织中，然后这些纳米颗粒作为佐剂或药物载体，以最大化冷冻传热过程、调节冷冻范围、改变冰球形成方向或防止周围健康组织被冷冻。此外，在冷冻手术期间引入纳米颗粒还可以帮助更好地成像肿瘤边缘以及冰球边缘。这种新疗法提出了许多关键的基础问题以及有待解决的实际问题。本综述致力于对由此涉及的多尺度基础相变传热问题进行全面综述。关注点将从细胞尺度的微观传热到组织层面。将讨论纳米颗粒对冷冻过程的一些相关热物理效应，如冰核增强、单细胞冷冻过程中的水传输等。将说明使用纳米颗粒改变组织 - 颗粒成分的热性质、调节冰球的生长方向和强度、在有或没有大血管的组织中实现适形肿瘤破坏等的冷冻手术热管理。同时，将总结纳米颗粒运输及其辅助药物递送的基础问题。将提出用于研究纳米冷冻手术期间整个组织或细胞区域的微/纳米尺度传热的理论建模以及实验方法。将概述纳米技术与冷冻手术结合时的一些潜在应用和可能的挑战。纳米冷冻手术有望帮助扩展纳米生物医学工程这一新兴前沿领域的边界。
