Rome Claire, Deckers Roel, Moonen Chrit T W
Laboratory for Molecular and Functional Imaging, UMR5231 CNRS, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Handb Exp Pharmacol. 2008(185 Pt 2):225-43. doi: 10.1007/978-3-540-77496-9_9.
The interaction of ultrasound with tissue leads to radiation pressure, heat generation, and cavitation. These phenomena have been utilised for local gene delivery, transfection and control of expression. Specially designed nanocarriers or adapted ultrasound contrast agents can further enhance local delivery by: (1) increased permeability of cell membranes; (2) local release of genes. Biological carriers may also be used for local gene delivery. Stem cells and immune cells appear especially promising because of their homing capabilities to lesion sites. Imaging methods can be employed for pharmacodistribution and pharmacokinetics. MRI contrast agents can serve as non-invasive reporters on gene distribution when co-delivered with the gene. They can be used to label nanocarriers and cellular transport systems in gene therapy strategies such as those based on stem cells. Finally, ultrasound heating together with the use of a temperature sensitive promoter allows a local, physical, spatio-temporal control of transgene expression, in particular when combined with MRI temperature mapping for monitoring and even controlling ultrasound heating.
超声与组织的相互作用会导致辐射压力、热生成和空化现象。这些现象已被用于局部基因递送、转染和表达控制。经过特殊设计的纳米载体或经过改良的超声造影剂可通过以下方式进一步增强局部递送:(1)增加细胞膜通透性;(2)局部释放基因。生物载体也可用于局部基因递送。干细胞和免疫细胞因其向损伤部位归巢的能力而显得特别有前景。成像方法可用于药物分布和药代动力学研究。当与基因共同递送时,磁共振成像(MRI)造影剂可作为基因分布的非侵入性报告分子。它们可用于标记基因治疗策略(如基于干细胞的策略)中的纳米载体和细胞转运系统。最后,超声加热与温度敏感启动子的使用相结合,可实现对转基因表达的局部、物理、时空控制,特别是在与MRI温度映射相结合以监测甚至控制超声加热时。