PLGA nanoparticles co-delivering MDR1 and BCL2 siRNA for overcoming resistance of paclitaxel and cisplatin in recurrent or advanced ovarian cancer

Title : PLGA nanoparticles co-delivering MDR1 and BCL2 siRNA for overcoming resistance of paclitaxel and cisplatin in recurrent or advanced ovarian cancer

Abstract:

The inherent or acquired resistance to paclitaxel and cisplatin, which are commonly used chemotherapeutic agents for ovarian cancer treatment, remains an important issue in chemotherapy of multidrug resistant ovarian cancer. Currently, it is still challenging to deal with the recurrent or advanced stage ovarian cancer. When drug efflux and anti-apoptotic pathways are highly interdependent and also involved in developing the resistance of multidrug resistant ovarian cancer, simultaneous inhibition of both pathways represents the potential targets to enhance the efficacy of chemotherapy. Herein, we introduce PLGA nanoparticles system as a “dual RNAi delivery system” to contain both MDR1 and BCL2 siRNA, which is designed for simultaneous inhibition of drug efflux and cell death defense pathways. In the present studies, siRNA-loaded PLGA nanoparticles efficiently elicit the simultaneous suppression of both genes, which consequently shows more enhanced drug-sensitivity than sole suppression of drug efflux or anti-apoptosis in the resistant ovarian cancer cells, owing to the interdependence of both pathways. Our siRNA-loaded PLGA nanoparticles for co-delivering MDR1 and BCL2 siRNA provide an efficient combination therapy strategy to overcome the chemoresistance of paclitaxel and cisplatin on the paclitaxel-resistant SKOV3-TR and cisplatin-resistant A2780-CP20 ovarian cancer respectively, as well as to expand the use of traditional chemotherapeutics to the treatment of recurrent or advanced ovarian cancer.

Audience take away:
• When drug efflux and anti-apoptotic pathways are highly interdependent and also involved in developing the resistance of multidrug resistant ovarian cancer, simultaneous inhibition of both pathways represents the potential targets to enhance the efficacy of chemotherapy .
• Our siRNA@PLGA nanoparticles, as a dual RNAi suppressor system on the MDR ovarian cancer cells, provide a combination therapy strategy to overcome the chomoresistance of paclitaxel and cisplatin on MDR SKOV3-TR and A2780-CP20 ovarian cancer.
• Our studies also suggest an efficient means to expand the use of traditional chemotherapeutics to the treatment of recurrent or advanced ovarian cancer. 

Biography:

Hyung Jun Ahn is a Principal Research Scientist of Biomedical Research Institute at Korea Institute of Science and Technology (KIST). He received his BS, MS, and PhD degrees from Seoul National University (Chemistry). After postdoctoral training under the supervision of Prof. Yigong Shi at the Department of Molecular Biology, Princeton University, Dr. Ahn joined a Senior Research Scientist, KIST in 2006. Dr. Ahn has been an Adjunct Professor at the Department of Biomedical Engineering in University of Science and Technology since 2010. Dr. Ahn’s research is concerned with biomaterials-based drug delivery, siRNA delivery, and molecular imaging technology.