1. High density lipoprotein nanoparticle as delivery system for radio-sensitising miRNA: An investigation in 2D/3D head and neck cancer models
- Author
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Parisa Badiee, Michelle Frances Maritz, Benjamin Thierry, Pouya Dehghankelishadi, Dehghankelishadi, Pouya, Maritz, Michelle F, Badiee, Parisa, and Thierry, Benjamin
- Subjects
high density lipoprotein nanoparticle ,radio-sensitiser ,MicroRNAs ,Head and Neck Neoplasms ,Cell Line, Tumor ,tumour spheroid ,microfluidics ,Pharmaceutical Science ,Humans ,Nanoparticles ,head and neck cancer ,Lipoproteins, HDL ,miRNA - Abstract
Refereed/Peer-reviewed Radiotherapy is one of the main treatment options for head and neck cancer patients. However, its clinical efficacy is hindered by both radiation induced side effects and radio-resistance. Radio-sensitising approaches with acceptable toxicity are being actively investigated. Among these, RNA therapeutics have great potentials as radio-sensitisers owing to their ability to target pathways specific to radio-resistance. However, their clinical translation is challenging due to delivery issues. Herein, we report the application of high-density lipoprotein nanoparticle (HDL NPs) as a biocompatible delivery system for a well-established radio-sensitising RNA, miR-34a. A simple/fast microfluidic based technique was used to prepare miR-34a-HDL NPs. Profiling of the radiation response in the UM-SCC-1 head and neck cancer cell line confirmed reduced metabolic activity and increased radiation induced apoptosis upon treatment with miR-34a-HDL NPs. The radio-sensitising properties of miR-34a-HDL NPs were further confirmed in a more biologically relevant co-culture spheroid model of head and neck cancer. Increased apoptotic activity and disrupted cell cycle were induced by miR-34a delivered by HDL NPs. The enhanced radio-biologic effects observed in both 2D and 3D models confirmed the utility of HDL NPs as an efficient delivery system for radio-sensitising RNA.
- Published
- 2021