The Study Of Mechanism Of Light-activated And Ultrasound-activated Hematoporphyrin Derivatives

A malignant tumor is one of the most dangerous diseases threatening human's health and life. It is estimated that in the 21st century the number of people round the world suffering from cancer will be a large increase .So how to treat tumors has become a significant problem in medical field. Among many antitumor therapies, more and more scholars focus their eyes on an effective and convenient approach, which is a combination of light and hematoporphyrin therapy or of ultrasound and hematoporphyrin therapy. Hematoporphyrin, as a special photo-sensitizer, shows preferential retention and a long time maintenance in tumor tissues compared with in the normal tissues. Ultrasound penetrates much deeper in biological tissues and is easier to focus without any harm to the normal tissues when compared to light. Because of this, this newly antitumor therapies by hematoporphyrin and ultrasound may be potentially useful for treating tumors located relatively deep in the body.Nowadays, scientists at home and abroad, especially Japanese scholar S.Umemura, have done many works on this, and have gained some results. But the use of sonochemical effects of ultrasound for cancer therapy has not been systematized, which is limited to the suspension of tumor cells and vivo tumors transplanted by certain animals. And few studies have been reported about the detailed mechanism of ultrasound reaction of hematoporphyrin. In order to find out the precise mechanism of it based on internal and external researches, combined with the National Science Fund item, according to S.Umemura' thinking, the author has done some further works on it.The author simplifies the molecule of hematoporphyrin by the Htlckel Molecular Orbital graph theory, which has been proved to be a more effective way than many advanced and sophisticated theoretical methods to solve electron systems ,andcalculates theoretically excitation and emission wavelengths, the results are consist with the experimental data. And then, we have designed a kind of isotropic light trap made from dense crown (n=1.61263), the properties of which are investigated. Experimental results show that the plot of output intensity vs input intensity is approximately linear, moreover experimental output intensity is always greater than input intensity. All this results indicate the light trap has good performance to collect light. This new type of light-collection is used to determine the relations of efficiency of ultrasonically activating hematoporphyrin illuminated by light with the light intensity ., exposure duration and the concentration of hematoporphyrin. Based on it, the threshold intensity of hematoporphyrin is measured to be 1.27+10-10 W/cm2 and 15.2+10-10 W/cm 2 when exposed to light .In addition, the sonoluminescence photographs taking in the experiment, have been a strong support to manifest that sonoluminescence produced in water has inadequate energy to activating hematoporphyrin though its peak is close to the absorption peak of hematoporphyrin. Ultrasonically induced cavitation produces nonequilibrium high temperature, emits shock waves, together with the cavitation energy in hematoporphyrin solution activating hematoporphyrin.At the same time, our results have suggested that 1, 3-diphenylisobenzofuran is a good choice for quenching single oxygen when hematoporphyrin is irradiated by light or ultrasound.The results of our work suggest that only sonoluminescence energy has not enough energy to activate hematoporphyrin. Cavitation energy without sonoluminescence energy may play a key role in activating hematoporphyrin, but the precise mechanism remains for further studies. What we have done provides a theoretical reference for the development of the sonodynamic therapy.