Laboratory IMF UMR 5231 CNRS/University Bordeaux, France.
J Control Release. 2011 Nov 7;155(3):442-8. doi: 10.1016/j.jconrel.2011.06.006. Epub 2011 Jun 12.
A novel two-step protocol for intracellular drug delivery has been evaluated in vitro. As a first step TO-PRO-3 (a cell-impermeable dye that displays a strong fluorescence enhancement upon binding to nucleic acids) encapsulated in thermosensitive liposomes was released after heating to 42°C. A second step consisted of ultrasound-mediated local permeabilization of cell membrane allowing TO-PRO-3 internalization observable as nuclear staining. Only the combination of two consecutive steps - heating and sonication in the presence of SonoVue microbubbles led to the model drug TO-PRO-3 release from the thermosensitive liposomes and its intracellular uptake. This protocol is potentially beneficial for the intracellular delivery of cell impermeable drugs that suffer from rapid clearance and/or degradation in blood and are not intrinsically taken up by cells.
一种新的两步法细胞内药物递释方案已经在体外进行了评估。作为第一步，在加热至 42°C 后，热敏感脂质体中包裹的 TO-PRO-3（一种细胞不可渗透的染料，与核酸结合后会显示出强烈的荧光增强）被释放出来。第二步是通过超声介导的细胞膜局部通透化，使 TO-PRO-3 能够内化，可观察到核染色。只有在 SonoVue 微泡存在的情况下，连续两步 - 加热和超声，才能导致模型药物 TO-PRO-3 从热敏脂质体中释放出来，并被细胞内摄取。该方案对于细胞不可渗透的药物的细胞内递释具有潜在的益处，这些药物在血液中容易快速清除和/或降解，并且本身不会被细胞摄取。
