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Archive > Volume 33 Issue 3 > 2026,33(3):288-295. DOI:10.3872/j.issn.1007-385X.2026.03.008 Prev Next
Basic Research
Circular nucleic acid aptamer-drug conjugates combined with CAR19-T/NK cells enhance cytotoxicity against acute lymphoblastic leukemia cells
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Abstract:
[Abstract] Objective: To investigate the enhanced cytotoxic effect of circular nucleic acid aptamer-drug conjugates (ApDC) combined with anti-CD19 chimeric antigen receptor T/NK (CAR19-T/NK) cells on Nalm6 leukemia cells. Methods: Database analysis was used to identify the marker protein tyrosine kinase 7 (PTK7) in leukemia cells. An aptamer targeting PTK7, sgc8, was designed and synthesized. Subsequently, two ApDCs were prepared: nucleic acid aptamer-conjugated gemcitabine (sgc8-GEM) and circular nucleic acid aptamer-conjugated gemcitabine (C-sgc8-GEM). Their stability was analyzed using agarose gel electrophoresis. Human peripheral blood T/NK cells were transfected with CD19-CAR overexpression lentivirus to construct CAR19-T and CAR19-NK cells. The binding affinity of sgc8 to Nalm6 cells was detected using flow cytometry. The cytotoxicity of sgc8-GEM, C-sgc8-GEM, and their combination with CAR19-T or CAR19-NK cells against Nalm6 cells was evaluated using CCK-8 assay and flow cytometry. Results: PTK7 mRNA was highly expressed in leukemia cells (P < 0.01). C-sgc8-GEM exhibited higher stability than sgc8-GEM, and sgc8-GEM exhibited more effective cytotoxicity against Nalm6 cells compared to GEM alone (P < 0.001). The combination of C-sgc8-GEM or sgc8-GEM with CAR19-T/NK cells showed significantly stronger cytotoxicity against Nalm6 cells than C-sgc8-GEM, sgc8-GEM, or CAR19-T/ NK cells alone (P < 0.001). Conclusion: The circular ApDCs combined with CAR19-T/NK cells were successfully developed. This dual-targeting strategy effectively increased the cytotoxicity against Nalm6 cells, providing a new treatment approach for acute lymphoblastic leukemia.
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