Research On Photosensitizers With Strong Penetrability And Cancer Targeting For Photodynamic Therapy

Photodynamic therapy?PDT?is based on reactive oxygen species?ROS?to kill cancer cells generated from the photochemical reactions between oxygen molecules and photosensitizers?PSs?gathered around the tumor tissues under light activation.Because of exhibitting good selectivity,low side effect and reproducibility,PDT has been one of the most advanced and promising research fields of Oncology in the world.However,these photosensitizers in present medical use still have several problems,week tissues penetration and poor tumor targeting,since could not be applied in PDT of deep tumor tissues.To solve these above problems,this paper introduce a novel compound photosensitizer,UCNPs@PS@HA,which cleverly combines upconversion nanoparticles?UCNPs?and hyaluronic acid?HA?,UCNPs could upconvert a lower energy photon into a higher energy photon through an anti-Stokes photoluminescence process and HA could specifically target CD44 over-expressing cancer cell.These compound photosensitizers are designed in order to be applied in deep tumor tissues for PDT.The thesis is divided into four parts.The first part is the preparation and characterization of compound photosensitizers of UCNPs@PS@HA.Porphyrin molecules are embeded into the porous on the surface of mesoporous silica coated UCNPs,then HA molecules are grafted covalently to its surface by carboxyl amine bond,finally the preparation of compound photosensitizers of UCNPs@PS@HA are completed.Then to detect the spectroscopy properties and singlet oxygen?¹O₂?production of compound photosensitizers through relevant Fluorescence spectrometer.The second part is to study the cell imaging and toxicological of above compound photosensitizer.Its cell toxicity is less than 20%in the absence of light,and PDT efficiency is between 40%and 50%under 980 nm near infrared light?NIR?,additionally,UCNPs@PS@HA displays good fluorescence emission under the inverted two-photon confocal microscopy,since it can be applied in biological imaging.The third part is to adjust the ¹O₂ yield of compound photosensitizers by regulating the fluorescence peak groups or emssion intensity of UCNPs and choosing different kinds of photosensitizers'molecule to load.Specifically,to change the type and proportion of doped-rare earth ions in UCNPs,and optimize a single photosensitizer or try mixing photosensitizers to load.The last part is to regulate the targeting ability of these compound photosensitizers.The molecular weight of HA may affect the molecular recognition ability as a targeting melocular.Therefore,we have prepared five kinds of UCNPs@PS@HA covalently grafted with different HA molecular weights?MW:5 Kto 1000 KDa?,then to detect HA targeting ability by these PDT efficiency under 980 nm NIR light.We successfully constructed the basic template of UCNPs@PS@HA compound photosensitizer,and on this basis,to prepare some differentiated customized compound photosensitizers by the regulation of UCNPs type,HA molecular weight and variety of porphyrin moleculars.Our work will provide the feasible improvement methods for the preparation of compound photosensitizers to impove the PDT efficiency.