High density lipoprotein nanoparticle as delivery system for radio-sensitising miRNA: An investigation in 2D/3D head and neck cancer models.

Autor: Dehghankelishadi P; Future Industries Institute and ARC Centre of Excellence Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Adelaide, SA 5095, Australia; UniSA Clinical and Health Sciences, University of South Australia, City West Campus, Adelaide, SA 5000, Australia., Maritz MF; Future Industries Institute and ARC Centre of Excellence Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Adelaide, SA 5095, Australia., Badiee P; Future Industries Institute and ARC Centre of Excellence Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Adelaide, SA 5095, Australia; UniSA Clinical and Health Sciences, University of South Australia, City West Campus, Adelaide, SA 5000, Australia., Thierry B; Future Industries Institute and ARC Centre of Excellence Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Adelaide, SA 5095, Australia; UniSA Clinical and Health Sciences, University of South Australia, City West Campus, Adelaide, SA 5000, Australia. Electronic address: benjamin.thierry@unisa.edu.au.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2022 Apr 05; Vol. 617, pp. 121585. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1016/j.ijpharm.2022.121585
Abstrakt: 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.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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