Probing Drug-cell Interaction By Atomic Force Microscopy

Probing drug-cell interaction is helpful to understand the mechanism of drugs, the ultramicrostructure of cells, their structure function relationsship, and also can provide information in nanoscale to evaluate different drug delive ry systems , so it becomes one of the hot topics in cell biology. Compared with conventional microscopic techniques, atomic force microscope (AFM) has many advantages such as xy resolution reaches the nanometer level, and z resolution is around 0.1 nm, the sample needs no complex pretreatment, not dependent on some staining chemicals. Not only topographical data could be reported, AFM can also collect many kinds of information from sample, such as elastic, electric charge and magnetism property. Utilizing the advantages of AFM, we investigated the effect of different drugs on cell. The main researches of this dissertation are summarized as follows:1. AFM study of the interaction between doxorubicin and cells. First, we investigated the effect of doxorubicin on normal and cancer cells.The results shows: the effect on cancer cells is stronger than that on normal cells. Based on this, we also investigated the morphological change of cells in nanoscale induced by liposomal doxorubicin and compared the results with free doxorubicin. The data shows that: cytotoxicity of free doxorubicin is higher than liposomal doxorubicin in vitro. This is helpful to evaluate these two ways of drug delivery.2. AFM study of the interaction between Chlorin e6 (Ce 6)and cells. In this section, changes in morphology, roughness and mechanical properties of Hela cells, exposed to the oxidative stress induced in the presence of Ce6 and light, were studied using AFM. The results demonstrated under illumination and Ce6, this process presented time and concentration depended effect as a marked drop in the cellular stiffness. This will help to understand the photodynamic therapy effect of Ce6.