Research On Responsive Nanomicelles For Chemotherapy And Immunotherapy

Cancer has become one of the major diseases which threaten human health.Anticancer drug such as doxorubicin,paclitaxel,docetaxel have some limitations including poor water solubility,short circulation time in vivo,toxic side effects,etc.The development of nanotechnology offers prospect for cancer treatment.Nanocarriers can increase the water solubility of drugs and achieve targeted drug delivery to tumor cells.In this paper,two nanomedicine delivery systems were developed,which could improve the water solubility of drugs and enhance the treatment efficacy and reduce their toxicity.Part I:TPGS₃₃₅₀-SS-DTX and TPGS₃₃₅₀-Fol were used to prepare micelles through thin film hydration.TPGS₃₃₅₀ prolonged the circulation time of the micelle in the blood.After micelle were accumulated at the tumor site by EPR effect,micelles entered into tumor cells through folate receptor-mediated endocytosis.Next,disulfide bonds in micelles was reduced by high level glutathione（GSH）in tumor cells,releasing drug quickly.Therefore,these micelles can enhance the efficient of treatment to cancer and reduce their toxic side effects.Part II:a novel micelle of PPA-Pep-DOX/PEG-Pep-DOX were fabricated.Among of them,the outer layer of PEG was used to prolong circulation time in body.The peptide of Pep could be cut off by a matrix metalloproteinase2（MMP2）overexpressing at the tumor site,shedding PEG and PPA and reducing the size of the micelle to facilitate micelles to be endocytosis by tumor cells.Moreover,shedding PPA could bind with PD-1 on the surface of T cells,competitively inhibiting PD-L1on the surface of tumor cells,causing immune response of T lymphocyte to activate the immune response in vivo.