1. Academic Validation
  2. Bosutinib high density lipoprotein nanoformulation has potent tumour radiosensitisation effects

Bosutinib high density lipoprotein nanoformulation has potent tumour radiosensitisation effects

  • J Nanobiotechnology. 2023 Mar 21;21(1):102. doi: 10.1186/s12951-023-01848-9.
Pouya Dehghankelishadi 1 2 Parisa Badiee 1 2 Michelle F Maritz 1 Nicole Dmochowska 1 Benjamin Thierry 3 4
Affiliations

Affiliations

  • 1 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.
  • 2 UniSA Clinical and Health Sciences, University of South Australia, City West Campus, Adelaide, SA, 5000, Australia.
  • 3 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. benjamin.thierry@unisa.edu.au.
  • 4 UniSA Clinical and Health Sciences, University of South Australia, City West Campus, Adelaide, SA, 5000, Australia. benjamin.thierry@unisa.edu.au.
Abstract

Disruption of the cell cycle is among the most effective approach to increase tumour cells' radio-sensitivity. However, the presence of dose-limiting side effects hampers the clinical use of tyrosine kinase inhibitors targeting the cell cycle. Towards addressing this challenge, we identified a bosutinib nanoformulation within high density lipoprotein nanoparticles (HDL NPs) as a promising radiosensitiser. Bosutinib is a kinase inhibitor clinically approved for the treatment of chronic myeloid leukemia that possesses radiosensitising properties through cell cycle checkpoint inhibition. We found that a remarkably high bosutinib loading (> 10%) within HDL NPs could be reliably achieved under optimal preparation conditions. The radiosensitisation activity of the bosutinib-HDL nanoformulation was first assessed in vitro in UM-SCC-1 head and neck squamous cell carcinoma (HNSCC) cells, which confirmed efficient disruption of the radiation induced G2/M cell cycle arrest. Interestingly, the bosutinib nanoformulation out-performed free bosutinib, likely because of the specific affinity of HDL NPs with tumour cells. The combination of bosutinib-HDL NPs and radiotherapy significantly controlled tumour growth in an immunocompetent murine HNSCC model. The bosutinib-HDL nanoformulation also enhanced the radiation induced immune response through the polarisation of tumour associated macrophages towards proinflammatory phenotypes.

Keywords

Bosutinib; Cell cycle; High density lipoprotein nanoparticle; Radiosensitiser; Reformulation.

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