A multi-storey DNA nanostructure containing doxorubicin and AS1411 aptamer for targeting breast cancer cells.

Herein, we presented a novel DOX-loaded multi-storey DNA nanostructure, including AS1411 aptamer as a targeting agent for treatment of target cells (MCF-7 and 4T1). Gel retardation test and fluorometric analysis were used to examine the construction of DNA nanostructure and loading of DOX in the complex. At pH 5.5 and 7.4, the release patterns of DOX from the prepared formulation were studied. Cell viability test was conducted to analyse the cell cytotoxicity ability of the DOX loaded multi-storey DNA nanostructure compared to free DOX in 4T1, MCF-7 (target) and CHO cells (non-target). Flow cytometry analysis was used to examine the DOX-loaded DNA nanostructure internalisation. Finally, the developed DOX-loaded multi-storey DNA nanostructure was tested in vivo to see if it could prevent tumour growth. The drug was released from the nanocomplex in a pH-related process (higher release in acidic pH compared to neutral pH). According to MTT assay, DOX-loaded DNA nanostructure damaged nucleolin positive cells while not significantly affecting nucleolin negative cells. The formulation was efficaciously internalised into target cells (4T1 and MCF-7), but not into non-target ones. Moreover, DOX-loaded DNA nanostructure can restrict tumour growth, increase survival rate, and accumulate significantly more in the tumour site than free DOX.

Design, synthesis and biological evaluation of novel imidazole-chalcone derivatives as potential anticancer agents and tubulin polymerization inhibitors.

Novel imidazole-chalcone derivatives were designed and synthesized as tubulin polymerization inhibitors and anticancer agents. The antiproliferative activity of the imidazole-chalcone was assessed on some human cancer cell lines including A549 (adenocarcinoma human alveolar basal epithelial cells), MCF-7 (human breast cancer cells), MCF-7/MX (mitoxantrone resistant human breast cancer cells), and HEPG2 (human hepatocellular carcinoma cells). Generally, the imidazole-chalcone derivatives exhibited more cytotoxicity on A549 cancer cells in comparison to the other three cell lines, among them compounds 9j' and 9g showed significant cytotoxicity with IC50 values ranging from 7.05 to 63.43 µM against all the four human cancer cells. The flow cytometry analysis of A549 cancer cells treated with 9g and 9j' displayed that these compounds induced cell cycle arrest at the G2/M phase at low concentrations and increased the number of apoptotic cells (cells in subG1 phase) at higher concentrations. They have also inhibited tubulin polymerization similar to combretastatin A-4 (CA-4). Annexin V binding staining assay in A549 cancer cells revealed that compound 9j' induced apoptosis (early and late). Finally, molecular docking studies of 9j' into the colchicine-binding site of tubulin presented the probable interactions of these compounds with tubulin.