Yaw Opoku Damoah
The University of Queensland, Australia
Title: Nanotheranostic lipoprotein-inspired zinc oxide-bound paclitaxel for enhanced anticancer photochemotherapy
Biography
Biography: Yaw Opoku Damoah
Abstract
With the emergence of nanotechnology, there is a pressing need for novel bio-friendly drug delivery systems which are capable of eliminating all the constraints related to traditional treatment regimens. Driven by this need, this work encompasses drug targeting via reconstituted High-Density Lipoproteins (rHDL), chemotherapy, photodynamic therapy and in vitro nano-inspired theranostics. Herein, we successfully fabricated zinc oxide-bound paclitaxel (ZnO/PTX) and packaged the photo-chemotherapeutic formulation into rHDLs via one-pot synthesis. The final rHDL mediated ZnO/PTX nanomedicine (rHDL/ZnO/PTX) shared a characteristic near-spherical shape and FTIR analysis proved that ZnO was successfully bound to PTX via hydrogen bonding. The PTX and ZnO drug release pattern was analyzed by HPLC and ICP-OES analysis, respectively. The results suggested that ZnO could remain intact in neutral medium but could gradually dissolve in acidic media to trigger the collapse of the nanoparticle. The in vitro antitumor efficacy on A549 cells was evaluated by MTT assay and flow cytometry. The final nanoparticle irradiated with UV light proved to be the most efficient treatment group. This was further confirmed by the quantitative and qualitative detection of Reactive Oxygen Species (ROS) which indicates the apoptotic ability. Confocal laser scanning microscopy was used to detect the presence of ROS and the resulting images suggested that rHDL/ZnO/PTX could produce significant quantities of ROS. Flow cytometry analysis was employed to confirm that the fluorescence was more conspicuous in cells that were irradiated with UV light as compared to those without UV irradiation. We further employed flow cytometry to evaluate the existence of apoptotic and necrotic cells after a period of treatment. Moreover, ZnO fluorescence was adapted to track intracellular trafficking, suggesting that rHDL/ZnO/PTX could be harnessed for UV light-mediated photo-chemotherapy while apolipoprotein A-I (apoA-I) could help facilitate the shuttling of drugs into cancer cells via SR-BI receptors. In addition, we demonstrated that ZnO could be used as a potential in vitro theranostic moiety which could mediate photodynamic therapy and pH-responsive drug delivery.