論文 - 詳細
| RRC ID | 75616 |
|---|---|
| 著者 | Dehghankelishadi P, Badiee P, Maritz MF, Dmochowska N, Thierry B. |
| タイトル | Bosutinib high density lipoprotein nanoformulation has potent tumour radiosensitisation effects. |
| ジャーナル | 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. |
| 巻・号 | 21(1) |
| ページ | 102 |
| 公開日 | 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 |
| リソース情報 | |
| 遺伝子材料 | mVenus-hGeminin(1/110) / pCSII-EF (RDB15271) mCherry-hCdt1(30/120)/ pCSII-EF (RDB15273) |