Hasan Akbaba1, Gülşah Erel-Akbaba2,3, Mustafa Kotmakçı2, Yücel Başpınar2. 1. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, 35100, İzmir, Turkey. hasan.akbaba@ege.edu.tr. 2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, 35100, İzmir, Turkey. 3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Izmir Katip Çelebi University, İzmir, Turkey.
Abstract
PURPOSE: Paclitaxel is a first-line drug for the therapy of lung cancer, however, drug resistance is a serious limiting factor, related to overexpression of anti-apoptotic proteins like survivin. To overcome this phenomenon, developing novel ultrasound responsive nanobubbles - nanosized drug delivery system- for the delivery of paclitaxel and siRNA in order to silence survivin expression in the presence of ultrasound was aimed. METHODS: Paclitaxel-carrying nanobubble formulation was obtained by modifying the multistep method. Then, the complex formation of the nanobubbles - paclitaxel formulation with survivin-siRNA, was examined in terms of particle size, polydispersity index, zeta potential, and morphology. Furthermore, siRNA binding and protecting ability, cytotoxicity, cellular uptake, gene silencing, and induction of apoptosis studies were investigated in terms of lung cancer cells. RESULTS: Developed nanobubbles have particle sizes of 218.9-369.6 nm, zeta potentials of 27-34 mV, were able to protect siRNA from degradation and delivered siRNA into the lung cancer cells. Survivin expression was significantly lower compared with the control groups and enhanced apoptosis was induced by the co-delivery of survivin-siRNA and paclitaxel. Furthermore, significantly higher effects were obtained in the presence of ultrasound induction. CONCLUSION: The ultrasound responsive nanobubble system carrying paclitaxel and survivin-siRNA is a promising and effective approach against lung cancer cells.
PURPOSE:Paclitaxel is a first-line drug for the therapy of lung cancer, however, drug resistance is a serious limiting factor, related to overexpression of anti-apoptotic proteins like survivin. To overcome this phenomenon, developing novel ultrasound responsive nanobubbles - nanosized drug delivery system- for the delivery of paclitaxel and siRNA in order to silence survivin expression in the presence of ultrasound was aimed. METHODS:Paclitaxel-carrying nanobubble formulation was obtained by modifying the multistep method. Then, the complex formation of the nanobubbles - paclitaxel formulation with survivin-siRNA, was examined in terms of particle size, polydispersity index, zeta potential, and morphology. Furthermore, siRNA binding and protecting ability, cytotoxicity, cellular uptake, gene silencing, and induction of apoptosis studies were investigated in terms of lung cancer cells. RESULTS: Developed nanobubbles have particle sizes of 218.9-369.6 nm, zeta potentials of 27-34 mV, were able to protect siRNA from degradation and delivered siRNA into the lung cancer cells. Survivin expression was significantly lower compared with the control groups and enhanced apoptosis was induced by the co-delivery of survivin-siRNA and paclitaxel. Furthermore, significantly higher effects were obtained in the presence of ultrasound induction. CONCLUSION: The ultrasound responsive nanobubble system carrying paclitaxel and survivin-siRNA is a promising and effective approach against lung cancer cells.
Entities:
Keywords:
lung cancer cell; nanobubble; paclitaxel; survivin-siRNA; ultrasound