Co-delivery Of Trx1shRNA And Doxorubicin By Folate-conjugated Cationic Liposome For The Treatment Of Hepatocellular Carcinoma

Chemotherapy plays an important role in the treatment of hepatocellular carcinoma(HCC). However, chemotherapy is often non-specific killing and easy to produce drugresistance. Therefore, the development of drug delivery system that can enhance thechemosensitivity of HCC cells and reduce the adverse effects to normal cells is urgentlyrequired. The co-delivery of gene drugs and chemotherapeutic agents for the treatment oftumors has become an important strategy in cancer treatment.Thioredoxin (Trx)1, a ubiquitously expressed small redox protein which has aconserved Cys-Gly-Pro-Cys redox catalytic site, plays critical roles in the regulation ofcellular redox homeostasis. It has been shown that Trx1is over expressed in a widevariety of human tumors including lung, pancreas, colon, gastric, breast and liver cancer.Trx1expression in cancer cells is associated with aggressive tumor growth, clinicalresistance to chemotherapeutic agents, which makes Trx1an attractive target for cancertherapy. Folate receptor is highly expressed in tumor cells, and Folate（FA）has theadvantages of high affinity and low immunogenicity. FA is an important targetingmolecule of tumor cells. In this paper, we have prepared a FA-conjugated cationicliposomes for co-delivery of Trx1shRNA and chemotherapeutic agent doxorubicin(DOX)to the hepatoma cancer cells to improve the sensitivity of tumor cells to chemotherapeuticagents.The completed work includes the following aspects:(1). The FA-conjugated cationic liposomes were prepared by the Gemini surfactants(C16-2-C16), DOPE, soyabean lecithin and FA-PEG-DOPE.(2). The FA-conjugated cationic liposomes showed high transfection efficiency. Trx1shRNA plasmid was transferred into cells successfully, and interfered with the expressionof Trx1to reduce the content of intracellular Trx1.(3). The FA-conjugated cationic liposome co-deliver Trx1shRNA and DOX to thetumor cells, while still exhibited high transfection efficiency and showed a sustained slowrelease of DOX.(4). The co-delivey system for Trx1shRNA and DOX resulted in a significantreduction in cell viability and a high apoptosis in Bel-7402cells. (5). The possible mechanism of co-delivey system for Trx1shRNA and DOX may bethe increase of the intracellular and intranuclear concentrations of DOX, whichsynergistically inhibited the cell viability and induced apoptosis in Bel7402cells.In summary, the FA-conjugated cationic liposomes can co-deliver gene drugs andchemotherapeutic agent to the hepatoma cancer cells to improve the sensitivity ofhepatocellular carcinoma cells to chemotherapeutic agents.