Aptamer RA16 Functionalized Drug-loaded DNA Tetrahedron For Targeted Therapy Of Non-small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death.The overall five-year survival rate of patients with non-small cell lung cancer is very low at 10 to 20 %,which has led to an increased need for their new treatment options.The aptamer-based method is a promising choice for early diagnosis and targeted therapy of non-small cell lung cancer,but the low stability of aptamer limits its application in vivo.Aptamer-functionalized DNA nanomaterials combine the unique selective recognition properties of aptamers and the stability and high-loading properties of nanomaterials,so they have been widely studied in the field of tumor-targeted therapy.In this study,the aptamer RA16,which has a high affinity for human non-small cell lung cancer cell line NCI-H460,was used as the targeting ligand to functionalize the DNA tetrahedron aptamer RA16-functionalized DNA tetrahedron(RA16-TD)was successfully synthesized.It has been found that RA16-TD has excellent biocompatibility,stability,hemolysis safety,and high drug-loading performance.Studies in living cells NCI-H460,BEAS-2B,4T1,and Hela showed that the binding specificity of RA16 was not affected by the connection with DNA tetrahedron,but RA16-TD could specifically bind to target cells with high internalization efficiency and strong targeting.RA16-TD loaded with epirubicin(EPI)can effectively kill tumor cells and has the potential to be used as a targeted delivery carrier for non-small cell lung cancer in vivo.Three-dimensional quantitative imaging and tissue RT-q PCR analysis confirmed that RA16-TD had good targeting and stability in vivo.RA16-TD loaded with epirubicin achieved a higher level of apoptosis in tumor-bearing mice,with a good tumor suppression effect and less liver damage,which has better prospects for targeted diagnostic and therapeutic applications in non-small cell lung cancer.In this study,the aptamer RA16 functionalized drug-loaded DNA tetrahedron enhanced the therapeutic effect of non-small cell lung cancer,confirmed that nucleic acid nanostructure modification has the potential to promote aptamer clinical application,and achieved high-efficiency and low-toxicity chemotherapy of lung cancer through non-small cell lung cancer specific targeting aptamer RA16,thus providing some references for the development of universal targeted diagnostic and therapeutic reagents for non-small cell lung cancer and alleviate the burden of lung cancer.