Targeting Treatment Of Bladder Cancer Using PTK7 Aptamer-Gemcitabine Conjugate

Bladder cancer(BC)is one of the most common urinary system malignancies.Gemcitabine(GEM)is one of the first-line chemotherapies for bladder cancer.However,these small molecular anticancer drugs(SMDs)have no tumor recognition ability and generally cause side effects,and have a low long-term response rate and high recurrence rate during the treatment of bladder cancer.Targeted transport of traditional SMDs to mediate cytotoxicity and avoid the systemic side effects is a challenge in the treatment of bladder cancer.Biomarker targeted functional nucleic acid aptamer-drug conjugates(APDCs)have become one of the most effective treatments.In this study,based on the protein tyrosine kinase 7(PTK7),a biomarker confirmed in bladder cancer that is overexpressed on the cell membrane surface in bladder cancer cells,a novel targeting system PTK7-GEMs was synthesized using a specific PTK7 aptamer and GEM.PTK7-GEMs could specifically bind to bladder cancer cells dependent on the expression levels of PTK7 and enter the target cell via the macropinocytosis pathway.GEM induced cytotoxicity after cleavage from PTK7-GEMs via an intracellular phosphatase.Moreover,PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in xenotransplanted subcutaneous tumor model.These results demonstrated that PTK7-GEMs is a successful biomarker targeted APDCs strategy to treat bladder cancer.