| Photodynamic therapy(PDT)is a well-established approach for the treatment of a variety of malignant tumors.As a non-porphyrin photosensitizer,hypericin is a potent natural photosensitizer with great potential in PDT,especially because of its high triplet quantum yield,minimal dark toxicity,tumor selectivity and high clearance rate from the host body.However,the poor water solubility of it can result in the drug cannot directly intravenous drug delivery.In addition,hypericin has an action spectrum that peaks around 595 nm,and the compound has virtually no absorption above 630 nm.These questions have limited the clinical PDT application of hypericinin some superficial cancers.In order to overcome the drawbacks of hypericin and promote them in the treatment of solid cancers,researchers have done much study in chemical modification and delivery system construction.In term of chemical modification,preparing hypericin and Mg2+ and Ca2+ metal ion complexes have gained much attention for the sake of convenient process,good activity and high yields.They improved the solubility of hypericin to some extent,as well as their absorption at longer wavelength.Recent years,inorganic nanoparticles as a new non-viral carriers have immense potential as a drug and biomolecule carrier system.Calcium phosphate is found to be one of the most promising of them primarily because of their excellent biocompatibility in a physiological environment and non-toxic degration product.Moreover,CaP has already been tested as a delivery vehicle for anticancer drugs.In the study of PDT,researchers has founded that PDT process may also be able to inhibit P-gp mediateddrug efflux,a drug efflux transporter,which is animportant determinant of tumor drug resistance.Thus,combination treatment of chemotherapyand PDT may not only increase anticanceractivity,overcome tumor drug resistance,but also can further enhance the anti-cancer activity of the PS.Based on the previous research,hypericin is investigated as a model photosensitizer in this research.To solve the problems that might be faced with in clinical applications,two major methods have been applied.On the one hand,a novel Hyp-metal ion complex was synthesized.This kind of complex improves the solubility and long wavelength absorption ability of Hyp.Moreover,it enhances the anti-cancer activity of the Hyp and has the specific characteristic of metal ion.On the other hand,we designed the proper method and system,based on the characteristic of Hyp and DHA,to synthesis new drug delivery system,including Hyp-incorporation CaP nanocarrier and Hyp/DHA-incorporation CaP nanocarrier together as follows:(1)Prepare the complex of Hyp and four metal ions.Determine the chemical structure of the complex and analyze the generation of ROSs of the complex when compared to pure Hyp and the specific characteristic of metal ion.Furthermore,study the anti-cancer efficacy of the novel complex.(2)CaP nanocarrier was prepared by co-precipitation method and it was good dispersion and high hydrophilic,the testing approaches,such as TEM,Zeta potential,XRD,FTIR,TG and so on,are applied to confirm that Hyp could be effectively incorporated into CaP nanocarrier,then,determine the maximum drug loading by UV-vis method,funally,under the same experimental conditions,the anti-cancer activity of the system was studied compared to pure Hyp.(3)CaP nanocarrier was prepared by co-precipitation method and it was good dispersion and high hydrophilic,the testing approaches,such as TEM,Zeta potential,XRD,FTIR,TG and so on,are applied to confirm that Hyp and DHA has been effectively incorporated into CaP nanocarrier,then,determine the maximum drug loading of Hyp and DHA by UV-vis and CD method respsctively,finally,under the same experimental conditions,the anti-cancer activityof the system was studied compared to Hyp-incorporation and DHA-incorporation system. |
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