Design And Synthesis Of High Molecular Weight Photosensitizer And Its Application In Photodynamic Therapy

Photodynamic therapy(PDT)has gradually become a new technology in the treatment of cancer.The three essential elements of PDT are light,oxygen and photosensitizer,among which photosensitizer plays a vital role.Most of the photosensitizers have superhydrophobic aromatic structure,poor water solubility,short-circulation time,?-? stacking effects induced aggregation-caused quenching and so on.Polymeric nanoparticles(NPs)have been extensively used to deliver most hydrophobic chemotherapeutic drugs or photosensitizers(PSs),improving the solubility of photosensitizers and elongating the circulation time.However,this strategy usually has problems with low loading content and undesired toxicity to normal tissues caused by the nontherapeutic and inert carrier.Carrier-free drug delivery strategy was developed to achieve high drug loading and avoid the side effects of the nontherapeutic carriers introduced.However,in the process of selfassembly of superhydrophobic photosensitizers to form NPs,their strong hydrophobic properties would also lead to the aggregation of PSs themselves instead of being loaded into the NPs efficiently,which greatly reduces the drug loading capacity and drug loading efficiency of NPS,and further reduces the PDT effect.In order to overcome the primary structural defects of clinical photosensitizers and the cytotoxicity problems caused by nanocarriers,porphyrin and boron fluoride dipyrrole(BODIPY),two representative photosensitizers,were designed to polymerize with reactive oxygen species(ROS)degradable flexible chains.A biodegradable and high molecular weight poly-photosensitizer was synthesized.On the one hand,the photosensitizer monomer is separated to form a spatial non-planar structure,which can inhibit the aggregation induced quenching caused by ?-? stacking,and improve the effect of photodynamic therapy.On the other hand,the polymerization strategy increases molecular weight to allow for long circulation in vivo and retention of tumor growth.In addition,water-soluble,degradable and targeted polyphotosensitizers can be synthesized by connecting water-soluble PEG,targeting HA or triphenyl phosphine after modification of the polymer structure,and a carrier-free selfsupporting drug system can be formed through self-assembly to realize the decarrier-free nano agents.The results showed that the singlet oxygen production of the two kinds of polyphotosensitizers was higher than that of their monomers,which confirmed that the polymerization strategy could effectively inhibit agglomeration and improve singlet oxygen production.In addition,the two kinds of poly-photosensitizers NPS could achieve ROS responsive degradation and tumor specific release.In conclusion,this polymerization strategy comprehensively solves the existing problems of hydrophobic PSS self-transfer system in the field of photodynamic therapy.