Nuclear-Targeted TAT-PZLL-D3 Co-Delivery DOX and p53 for Chemotherapy Resistance of SCLC

Small cell lung cancer (SCLC) accounts for 13% ~ 15% of lung cancer. It is a subtype with high malignancy and poor prognosis. Almost all patients with SCLC will inevitably have drug resistance and tumor recurrence, which has become an urgent problem in the treatment of SCLC. Nuclear-targeted drug delivery system, which enables intra-nuclear release of anticancer drugs, is expected to address this challenge. In this study, based on transactivator of transcription (TAT)’s active transport property to the nucleus, we developed a high-efficiency nucleus-targeted co-delivery vector that delivers genes and drugs directly into the nucleus of A549 cells. The system is based on a poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3) with TAT modified on the surface of carrier. In vitro studies showed that DOX and p53 could can be effectively transported to the nucleus and kill the cancer cells. Thus, such deliver system would bypass the drug resistance and tumor recurrence problem.