Institute of Micro and Nanomaterials, University of Ulm, Germany.
J Control Release. 2010 Dec 1;148(2):131-4. doi: 10.1016/j.jconrel.2010.10.010. Epub 2010 Oct 8.
Transmembrane diffusion imposes fundamental limits to the uptake of cytostatic drugs executing their function intracellularly. Here, we report that transmembrane convection-a mechanism exploiting the effect of moderately intense 670nm laser light on the density and viscosity of nanoscopic interfacial water layers (IWL) in the cell-forces cancer cells to uptake high doses of cytostatic drugs in a short time. Transmembrane convection is a viable alternative to established uptake forms (i.e., it works complementary to diffusive processes) and breaks the limits imposed by diffusion. We demonstrate the potency of the method in human cervical cancer cells, HeLa, using the anticancer compounds doxorubicin (DOX), methotrexate (MTX) and epigallocatechin gallate (EGCG). The method is applicable to virtually the entire chemotherapeutic arsenal and is expected to help overcome multidrug resistance in cancer cells.
跨膜扩散对细胞内执行功能的细胞毒性药物的摄取施加了基本限制。在这里,我们报告了跨膜对流——一种利用适度强的 670nm 激光对细胞中纳米级界面水层(IWL)的密度和粘度的影响的机制——迫使癌细胞在短时间内摄取高剂量的细胞毒性药物。跨膜对流是一种可行的替代现有摄取形式的方法(即,它与扩散过程互补),并打破了扩散施加的限制。我们使用抗癌化合物阿霉素(DOX)、甲氨蝶呤(MTX)和表没食子儿茶素没食子酸酯(EGCG)在人宫颈癌细胞 HeLa 中证明了该方法的效力。该方法几乎适用于整个化疗武器库,并有望帮助克服癌细胞中的多药耐药性。