RRC ID 75616
Author Dehghankelishadi P, Badiee P, Maritz MF, Dmochowska N, Thierry B.
Title Bosutinib high density lipoprotein nanoformulation has potent tumour radiosensitisation effects.
Journal J Nanobiotechnology
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.
Volume 21(1)
Pages 102
Published 2023-3-21
DOI 10.1186/s12951-023-01848-9
PII 10.1186/s12951-023-01848-9
PMID 36945003
PMC PMC10028769
MeSH Aniline Compounds / pharmacology Animals Antineoplastic Agents* / pharmacology Head and Neck Neoplasms* / drug therapy Head and Neck Neoplasms* / radiotherapy Mice Protein Kinase Inhibitors / pharmacology Protein Kinase Inhibitors / therapeutic use Squamous Cell Carcinoma of Head and Neck / drug therapy Squamous Cell Carcinoma of Head and Neck / radiotherapy
IF 6.518
DNA material mVenus-hGeminin(1/110) / pCSII-EF (RDB15271) mCherry-hCdt1(30/120)/ pCSII-EF (RDB15273)