This project proposes application of nanoporous materials for targeted intracellular drug delivery. In particular, silica nanotubes and mesoporous silica nanoparticles hydrophobically modified inside and with multifunctional exterior modification will be investigated for employing the hydrophobicity switching mechanism to intracellular transfection of small drug molecules and nucleic acids. In this mechanism, the hydrophobic interior holds the loaded 'drug'but promptly releases it when in contact with the cell membrane, where phospholipids wet the pores by decorating their hydrophobic walls and allowing cargo diffusion out directly into the cytoplasm. Different cargo molecules can be loaded into the nanopores with similar efficiency and the cargo transfection proceed into the cytoplasm without need for endocytosis. When equipped with ligands on the exterior for specific cell recognition, such nanotubes provide a targeted drug delivery system with anticipated minimal intrinsic cytotoxicity. This proof- of-concept project will be focusing on investigating in vitro delivery of two small drug molecules, doxorubicin and paclitaxel and short strand 'therapeutic nucleic acids'(TNA) into cancerous cell lines that are targeted by one of three ligands, folic acid, EpCAM and HER2.
This project proposes utilization of new hybrid nanomaterials for targeted drug delivery that can be applied for drug delivery formulations in treatment of various diseases including cancer. The anticipated advantage over other formulations for drug delivery is in a universal delivery mechanism with need for endocytosis allowing targeted delivery of drugs of different compositions and anticipated low intrinsic cytotoxicity of the delivery system itself.
|Dahal, Eshan; Curtiss, Jessica; Subedi, Deepak et al. (2015) Evaluation of the catalytic activity and cytotoxicity of palladium nanocubes: the role of oxygen. ACS Appl Mater Interfaces 7:9364-71|