Smart Aptamer Drug Delivery System Based On I-motif And DNA Tetrahedron For Inhibition Of Cervical Cancer

Traditional chemotherapeutic drugs occupy an essential position in the clinical treatment of tumors,but due to the lack of specificity to specific tumor sites,they often lead to severe systemic toxic side effects.Active targeting ligand-mediated drug delivery systems may result in undesirable non-specific uptake due to their receptors being expressed at low levels in normal tissue cells.Therefore,in this study,a pH-activated smart aptamer was constructed by introducing the i-motif into the Sgc8 c,and further coupling it with DNA tetrahedra to improve the stability and drug loading of the drug delivery system.The drug delivery system is used to deliver Dox with high specificity.In the physiological pH environment,the i-motif is a loose chain,which limits the formation of the Sgc8 c targeting loop and keeps the smart aptamer drug delivery system in the blood circulation and physiological tissue in a targeted inactive state.In the tumor microenvironment,i-motif forms a compact tetrameric structure and mediates Sgc8 c to generate a recognition loop capable of binding to the target,realizing the pH-activated targeting function selective uptake of Dox at the tumor.The synthesis was verified by PAGE,DLS and AFM.The results of PAGE and cytotoxicity showed apt/TDNs had good serum stability and biocompatibility.The PAGE,CD spectroscopy and fluorescence spectrophotometry results verified that smart aptamer and apt/TDNs have good pH-responsive properties.It was proved at the cytological level that apt/TDNs had an pH-activated targeting function and could achieve pH-dependent differences.In the multicellular tumor spheroids,it was proved apt/TDNs have pH-dependent tumor penetration ability,and have good tumor tissue penetration and accumulation ability.Their ability to deliver Dox was subsequently explored,and the results demonstrated that apt/TDNs had pH-dependent Dox delivery properties.Finally,its anti-tumor effect was investigated,and the results showed that apt/TDNs@Dox could deliver Dox into the depths of tumor tissue,exerting a practical anti-tumor effect and pro-apoptotic effect.Moreover,it can significantly improve Dox toxicity to cells at physiological pH.In conclusion,the smart aptamer drug delivery system we constructed provides a new idea and method for precise tumor targeting,and shows application prospects and potential in improving the toxicity and side effects of traditional chemotherapeutic drugs and enhancing targeting and efficacy.