Effect of the combined binding of topotecan and catechin/protocatechuic acid to a pH-sensitive DNA tetrahedron on release and cytotoxicity: Spectroscopic and calorimetric studies

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 314; p. 124179
• Main Authors: Wang, Lu, Liu, Jie, Wang, Xiangtai, Li, Xinyu, Zhang, Xinpeng, Yuan, Lixia, Wu, Yushu, Liu, Min
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.06.2024
• Subjects: Catechin - pharmacology; Chemotherapy drug; Combination therapy; DNA - chemistry; Hydroxybenzoates - pharmacology; Interaction; Natural polyphenol; pH-sensitive DNA tetrahedron; Topotecan - adverse effects; Chemotherapy drug; Combination therapy; Interaction; Natural polyphenol; pH-sensitive DNA tetrahedron
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2024.124179

[Display omitted] •A pH-sensitive DNA tetrahedron (MUC1-TD) was used to co-deliver TPT and CAT/PCA.•The presence of CAT or PCA weakened the binding of TPT to MUC1-TD.•Acid pH and CAT/PCA, especially PCA, improved the release of TPT loaded by MUC1-TD.•CAT enhanced the cytotoxicity of TPT loaded by MUC1-TD on A549 cells more than PCA.•The protective effect of CAT/PCA reduced the damage of TPT to L02 cells. The therapeutic efficacy of chemotherapy drugs can be effectively improved through the dual effects of their combination with natural polyphenols and the delivery of targeted DNA nanostructures. In this work, the interactions of topotecan (TPT), (+)-catechin (CAT), or protocatechuic acid (PCA) with a pH-sensitive DNA tetrahedron (MUC1-TD) in the binary and ternary systems at pHs 5.0 and 7.4 were investigated by fluorescence spectroscopy and calorimetry. The intercalative binding mode of TPT/CAT/PC to MUC1-TD was confirmed, and their affinity was ranked in the order of PCA > CAT > TPT. The effects of the pH-sensitivity of MUC1-TD and different molecular structures of CAT and PCA on the loading, release, and cytotoxicity of TPT were discussed. The weakened interaction under acidic conditions and the co-loading of CAT/PCA, especially PCA, improved the release of TPT loaded by MUC1-TD. The targeting of MUC1-TD and the synergistic effect with CAT/PCA, especially CAT, enhanced the cytotoxicity of TPT on A549 cells. For L02 cells, the protective effect of CAT/PCA reduced the damage caused by TPT. The single or combined TPT loaded by MUC1-TD was mainly concentrated in the nucleus of A549 cells. This work will provide key information for the combined application of TPT and CAT/PCA loaded by DNA nanostructures to improve chemotherapy efficacy and reduce side effects.