Studies Of Activatable Nano-photosensitizers Based On Fluorescein Derivatives

Photodynamic therapy is a new type of tumor treatment method.Clinical photodynamic therapy photosensitizers lack the ability to distinguish tumor tissues from healthy tissues,and patients need to be protected from light during treatment.The development of a photosensitizer specifically activated by tumor tissue has important scientific significance and application value.Tumor tissue has a microenvironment that is different from healthy tissue.The use of tumor microenvironment to develop activatable photosensitizers is a hot spot of current research.Based on the advantages of nanotechnology and the unique properties of a class of fluorescein photosensitizers with thermally activated delayed fluorescence（TADF）,this thesis has carried out research on two types of nano-photosensitizers which can be activated by specific biological species in the tumor microenvironment.Firstly,the photosensitive molecule DCF-MPYM-DA,which is hydrophobic,was designed and synthesized with activatable fluorescence and PDT effect by using the FDA-certified amphiphilic macromolecule vitamin E polyethylene glycol succinate（TPGS）through self-assembly.When the organic polymer nanomicelle was formed,DCF-MPYM-DA was encapsulated inside of the obtained nanomicelle photosensitizer TPGS@DCF-DPYM-DA.The nano-photosensitizer TPGS@DCF-DPYM-DA was in the"off"state of fluorescence and photodynamic efficiency before entering tumor cells.When the nano-photosensitizer reaches the tumor cells,the combined action of reactive oxygen species（ROS）and esterase in the tumor microenvironment can quickly turn on the photodynamic therapy and fluorescence functions of the nano-photosensitizer.The nano-photosensitizer is applied to the photodynamic therapy of breast cancer cell MCF-7.The results of MTT toxicity analysis show that for breast cancer cell MCF-7,TPGS alone is not enough to kill,while the effect of PDT of the nano-photosensitizer is significant,and the half inhibitory concentration(IC₅₀)is 131μg/m L.Secondly,based on the fluorescein derivative bio-thiol probe DCF-MPYM-thiol reported by the research group,TPGS was employed to form organic polymer nanomicelles through self-assembly to encapsulate DCF-MPYM-thiol.The obtained nano-photosensitizer,named as TPGS@DCF-DPYM-thiol,was in the"off"state of fluorescence and photodynamic efficiency before entering tumor cells.When the nano-photosensitizer reached the tumor cells,the reactive oxygen species（ROS）and glutathione（GSH）in the tumor cells worked together to quickly turn on the photodynamic therapy and fluorescence functions.Because GSH was consumed during the activation process,the nano-photosensitizer achieved a better therapeutic effect than the previous nano-photosensitizer TPGS@DCF-DPYM-DA in the PDT of cancer cells MCF-7with the half inhibitory concentration(IC₅₀)of 80μg/m L.In summary,this thesis used an amphiphilic polymer TPGS as the monomer of nanomicelles which self-assembled with two molecular photosensitizers to prepare two activatable nano-photosensitizers TPGS@DCF-DPYM-DA and TPGS@DCF-DPYM-thiol.These two nano-photosensitizers achieved excellent therapeutic effect in the photodynamic therapy of tumor cells.