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[Display omitted] • A DNA tetrahedron linked with the targeting aptamer MUC1 (MUC1-TD) was constructed. • Daunorubicin (DAU) and acridine orange (AO) intercalatively bound to MUC1-TD. • The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. • The combined DAU and AO had a synergistic cytotoxicity on drug-resistant cells. • The loading of MUC1-TD augmented the cytotoxic effects of DAU and AO. Chemotherapy–phototherapy (CTPT) combination drugs co-loaded by targeted DNA nanostructures can achieve controlled drug delivery, reduce toxic side effects and overcome multidrug resistance. Herein, we constructed and characterized a DNA tetrahedral nanostructure (MUC1-TD) linked with the targeting aptamer MUC1. The interaction of daunorubicin (DAU)/acridine orange (AO) alone and in combination with MUC1-TD and the influence of the interaction on the cytotoxicity of the drugs were evaluated. Potassium ferrocyanide quenching analysis and DNA melting temperature assays were used to demonstrate the intercalative binding of DAU/AO to MUC1-TD. The interactions of DAU and/or AO with MUC1-TD were analyzed by fluorescence spectroscopy and differential scanning calorimetry. The number of binding sites, binding constant, entropy and enthalpy changes of the binding process were obtained. The binding strength and binding sites of DAU were higher than those of AO. The presence of AO in the ternary system weakened the binding of DAU to MUC1-TD. In vitro cytotoxicity studies demonstrated that the loading of MUC1-TD augmented the inhibitory effects of DAU and AO and the synergistic cytotoxic effects of DAU + AO on MCF-7 cells and MCF-7/ADR cells. Cell uptake studies showed that the loading of MUC1-TD was beneficial in promoting the apoptosis of MCF-7/ADR cells due to its enhanced targeting to the nucleus. This study has important guiding significance for the combined application of DAU and AO co-loaded by DNA nanostructures to overcome multidrug resistance. [ABSTRACT FROM AUTHOR]

The combined application of polyphenols and anticancer drugs may be of great help to current cancer treatment. In this paper, the individual and combined interactions of oxyresveratrol (OXY)/piceatannol (PIC) and mitoxantrone (MIT) with human serum albumin (HSA) in phosphate buffer of pH 7.4 were studied by multi-spectroscopic techniques and molecular docking. The quenching mechanism of HSA by OXY, PIC and MIT was determined by fluorescence quenching experiments and UV difference spectra. The binding location of the three ligands on HSA was identified by site marking fluorescence spectra, synchronous fluorescence spectra, and molecular docking. For the OXY/PIC/MIT + HSA binary system and the OXY/PIC + MIT + HSA ternary system, the thermodynamic parameters were obtained. The results indicated the competitive binding of OXY/PIC and MIT to HSA. The driving forces in the binding process were discussed. The circular dichroism spectroscopy and dynamic light scattering were employed to investigate the effects of OXY/PIC/MIT single drug and OXY/PIC + MIT combined drugs on the secondary structure and particle size of HSA. The effects of drug combination and HSA interaction on the in vitro cytotoxicity against HeLa cells were determined by MTT assay. The results would provide a theoretical basis for the combined application of polyphenols and traditional anticancer drugs. Unlabelled Image • The quenching mechanism of HSA by OXY, PIC or MIT was static quenching. • The binding affinity with HSA decreased in the order of OXY > PIC>MIT. • OXY/PIC and MIT mainly competitively bound to subdomain IIA of HSA. • Drug-protein binding affected the secondary structure and particle size of HSA. • Drug combination and HSA complex demonstrated enhanced cytotoxicity. [ABSTRACT FROM AUTHOR]

• AS1411-DNA nanotrains (AS1411NTrs) were constructed by hybridization chain reaction (HCR). • DOX, EPI and DAU interacted with AS1411NTrs through the intercalative binding mode. • The constructed AS1411NTrs had high drug payload capacity. • The drug release from AS1411NTrs followed first-order release model. • The drug-loaded AS1411NTrs could target to specific cancer cells. As one of the most promising drug delivery carriers, self-assembled DNA nanostructures are characterized of well-defined sizes, excellent biocompatibility, high drug loading and ability to control drug release. Studying the interactions between anticancer drugs and DNA nanostructures can help to associate microstructure-drug loading-release rate-therapeutic effect. Herein AS1411 aptamer-tethered DNA nanotrains (AS1411NTrs) were constructed and used as anthracyclines carrier with high payload for targeted delivery. The bindings of doxorubicin (DOX), epirubicin (EPI), and daunorubicin (DAU) to AS1411NTrs were investigated by isothermal titration calorimetry and fluorescence spectroscopy, and thermodynamic parameters were obtained. The high drug payload capacity of AS1411NTrs was verified by the large number of binding sites (~20). The binding mode was determined by differential scanning calorimetry and potassium iodide (KI) quenching experiments. The release experiment data showed that DNase I facilitated drug release and the release followed the first-order kinetic model. MTT cell viability assay demonstrated that the drug-loaded AS1411NTrs had significantly higher cytotoxicity against target HeLa cells than normal human liver L02 cells. These findings revealed that AS1411NTrs had high payload and targeted release capacity for DOX, EPI, and DAU. This result can provide a theoretical basis for constructing reasonable DNA nanostructures based on drug carriers. Image, graphical abstract [ABSTRACT FROM AUTHOR]