Synthesis And Application Of Poly-photosensitizers For Photodynamic Therapy

In recent years,photodynamic therapy has gradually become a new method in cancer treatment.Photodynamic therapy consists of light,oxygen and photosensitizer,among which photosensitizer plays a crucial role.Tetrapenyl porphyrin?TPP?,as a common photosensitizer,has the disadvantages of poor water solubility,short cycle time,easy accumulation and aggregation caused quenching?ACQ?.In order to overcome the structural defects of TPP,this thesis designed and synthesized biodegradable photosensitizer with high molecular weight,which was used in the treatment of cancer cells The water-soluble cationic polyporphyrins were also designed to encapsulate genes to achieve an efficient and synergistic treatment method in photodynamic therapy and gene therapy.In the first part,the degradable polyporphyrin?pTPP?was obtained by the crosslinking polymerizationofROSdegradablethioketal-diaminewith meso-tetra?4-carboxyphenyl?porphine porphyrin,and then encapsulated with PEG-PLA to prepare nano-drug pTPP NP.It is found by UV characterization that the singlet oxygen yield of pTPP increases significantly compared with TPP monomer due to the avoidance of?-?accumulation.Cell experiments shows that pTPP NP has the enhanced phototoxicityas well as the excellent therapeutic effect towards cancer cells.In the second part,the A₂B₂-TPP monomer with carboxyl groups and alkyne groups was designed and synthesized.The polyporphyrin backbone was obtained by the dehydration polycondensation of carboxyl group and thioketal-diamine.The amino group was introduced into the polymer side chains by the click reaction of alkyne groups and azide groups.Since amino group is positively charged in physiological pH,it can be used to condense genes with negative charges via electrostatic interaction.The application of non-toxic photosensitizers to gene delivery can avoid the cytotoxicity which is commonly found in gene vectors.In addition,the water-soluble amino group significantly enhances the solubility of the cationic porphyrin polymers in water,which can be used as a carrier-free nano drug delivery system.The combination of such properties makes it more effective in cancer treatment.