Tumor Therapy And Diagnosis Based On Enzyme-responsive Drug Control Release Carrier Of Peptide

Cancer has been one of the threats to human health all the time.In the traditional chemotherapy process,although chemical drugs can effectively kill cancer cells,chemical drugs lack specific targeting of cancer cells.During the treatment process,they can affect normal cells.Therefore,scientists have vigorously developed many drug carriers for tumor treatment and diagnosis.Among these drug carriers,peptide-based nanocarriers,due to their good biocompatibility and biodegradability,show advantages over other drug carriers.In addition,by flexibly designing the sequence of the peptides,the drugs with different characteristics can be targeted to the tumor area.Subsequently,peptide-based nanocarriers control drugs release and reduces side effects.In addition,in order to solve the shortcomings of chemotherapy,photodynamic therapy(PDT)has been vigorously developed as a new type of treatment.The advantage of PDT is that it can be repeated treatment by light.However,the shortcoming of PDT is that the small scope and short of reactive oxygen species(ROS)that produced by the photosensitizer.Moreove,photosensitizers’ hydrophobic properties easily lead to aggregation-caused quenching(ACQ),which is not conducive to PDT and fluorescence imaging.Therefore,it is of great significance to transport photosensitizers to subcellular organelles or develop highly effective photosensitizers.And In view of these,the work of this paper is mainly in the following four aspects:In Chapter 1,we briefly reviewed the application of peptide drug carriers,enhanced PDT strategies,and aggregation-induced emission(AIE)fluorescent molecules in tumor treatment and imaging.In Chapter 2,we synthesized an enzyme-responsive chimeric peptide,it can form nanomicelles in water through the amphiphilicity.The nanomicelles can effectively transport photosensitizers into cancer cells.Because the lysosomes of cancer cells overexpress cathepsin B,and the enzyme can recognize the sequence GFLG,the micelles are disintegrated by enzymesand.The photosensitizer and doxorubicin(DOX)are released.The photosensitizer can effectively enrich mitochondria under the guidance of triphenylphosphine(TPP)and exert the effect of enhancing PDT.Finally,achieving the purpose of chemical-photodynamic therapy.In Chapter 3,we successfully bonded an AIE fluorescent molecule that emits red light to the peptide,it can form nanomicelles in water through the amphiphilicity.The nanomicelles can be effectively transported and endocytosed by cancer cells in the vivo.Then the nanomicelles are disintegrated by cathepsin B which overexpressed by the lysosome of cancer cells,and the enzyme can recognize the sequence GFLG,the AIE fluorescent fragments are released.The fragments aggregate through its hydrophobicity and emit a lot of red fluorescence,achieving the purpose of red light imaging of tumor cells.In Chapter 4,we designed an AIE photosensitizer that emits near-infrared light.The photosensitizer can be wrapped by peptide nanomicelles and effectively targeted to the cancer cell.Then the sequence GFLG of nanomicelles are disintegrated by cathepsin B which overexpressed by the lysosome of cancer cells,the photosensitizer is released.Subsequently,the photosensitizer emits near infrared fluorescence and exerts the PDT effect under light to kill cancer cells,achieving the purpose of guiding PDT through biofluorescence imaging.