Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures

Abstract

Paclitaxel (PTX) is an effective drug against diseases such as lung cancer, ovarian cancer, and breast cancer. However, multidrug resistance limits the clinical applications of this drug. Tetrahedral DNA nanostructures (TDNs) offer great promise as a drug delivery candidate. In our study, we prepared TDNs that were subsequently loaded with PTX (PTX/TDNs). The cytotoxicity of PTX/TDNs and PTX alone on non-small cell lung cancer (NSCLC) cells (A549) and the PTX-resistant cell line (A549/T) was determined using a cell count kit-8 (CCK-8) assay. PTX/TDNs exerted strong lethality on both cell lines. Moreover, drug resistance was overcome. Furthermore, the mechanisms used by PTX/TDNs to overcome drug resistance were studied. The expression of mdr 1 gene and P-glycoprotein (P-gp) in A549/T was found to be downregulated, thus indicating that TDNs serve as a P-gp inhibitor. We also showed that PTX/TDNs killed cancer cells via apoptosis. Thus, PTX/TDNs have great potential for use as a nanodelivery system for the treatment of PTX-resistant NSCLC.