Synthesis And Antitumor Activity Of Host - Guest Inclusion Compound Of Cyclodextrin - Polyamine Phthalocyanine

Photodynamic therapy (PDT) is a well-established approach for the treatment of a variety of malignant tumors. Phthalocyanine (Pc), as a typical representative of the second generation photosensitizer, most widely used in PDT because of strong absorption in the phototherapeutic window, high molar extinction coefficient, high singlet oxygen generation efficiency. The poor water solubility of Pcs can result in the drug cannot directly intravenous drug delivery. In addition, Pcs are ofen formed aggregate in the physiological environment and then lead to the photosensitive activity significantly reduced. These questions limit the PDT application of Pcs to a great degree.Studies have shown that the method, preparation of the host-guest complexes of cyclodextrin (CD) and Pc, can greatly improve the solubility of Pc in aqueous solution, but CD-Pc host-guest complexes have the low stability, and the inclusion manner and mechanism were not clear. In order to solve the above question, this article selects2(3),9(10),16(17),23(24)-tetra-(((2-(diethylamino) ethylamino) methyl) phenoxy) phthalocyanine zinc (Ⅱ) as the guest molecular, α-CD, P-CD, hydroxypropyl-β-CD (HP-β-CD) and y-CD as the host molecular, through4:1orderly side chain inclusion manner to synthesis the stability of CD-Pc host-guest inclusion compound. Base on the previous work, preparation a serious of (CD)4-ZnPc host-guest complexes to improve solubility in aqueous solution and photosensitive anti-tumor activity. The main research content as follow:(1) Prepared a series of CD-ZnPc complexes, with CD and ZnPc as different ratio. The best inclusion ratio was4:1by the UV-vis spectroscopy detection. The structure of (CD)4-ZnPc complexes were characterized through thermal analysis and infrared spectrum.(2) According to the molecular dynamics simulation proved the formation of (CD)4-ZnPc host-guest complexes at micro level. In addition, the spatial orientation of CD, binding energy and the parameter of hydrogen bonding were also researched.(3) The photophysical chemical property and the photosensitive activity of ZnPc and (CD)4-ZnPc complexes were detailed studied. The drugs of (CD)4-ZnPc and ZnPc have great security through the dark-toxicity, and excellent photo-activity through the morphological changes and Hoechst33342nucleus chromatin changes. The photosensitive anti-tumor activity is (CD)4-ZnPc> ZnPc, among (HP-β-CD)4-ZnPc most, detected by the reactive oxygen detection, HeLa cellular uptake rate and light-toxicity.(4) The degree of binding energy and the photosensitive anti-tumor activity of (CD)4-ZnPc complexes were compared, then obtained CD-ZnPc host-guest complex with prospecting application in PDT-(HP-β-CD)4-ZnPc.