Sensitive organelles of U251 MG glioblastomas to boron neutron capture therapy

The micro-distribution of boron compounds within cells influences the effectiveness of boron neutron capture therapy (BNCT) in killing tumor cells. Boron neutron capture therapy-sensitive organelles within the range of α particles and ⁷Li recoil nuclei can enhance killing effects on tumor cells. However, comprehensive studies on the sensitive organelles to BNCT are currently lacking. In the present study, we explored the sensitivity of organelles in U251 MG glioblastomas to BNCT. Trypan blue exclusion assay, the level of autophagic proteins, cell counting kit-8, and clonogenic formation assay were used to evaluate the sensitivity of the cellular membrane, the endoplasmic reticulum, the mitochondria, and the cell nuclei of U251 MG glioblastomas to BNCT (¹⁰B atoms of L-4-boronophenylalanin capture neutrons). Boron neutron capture therapy induced a trypan blue exclusion rate of 93.33%, no changes in the levels of LC3-II and Beclin-1, a survival rate of 77.78%, and reproductive death of 90.25% in U251 MG glioblastomas. These results indicate a hierarchical sensitivity of U251 MG glioblastoma organelles to BNCT ranked as the cell membrane (the endoplasmic reticulum) < the mitochondria < and the cell nucleus. Reproductive death, the main type of U251 MG glioblastoma death induced by BNCT, is attributed to the shortening of the S phase duration. The comprehensive understanding of sensitive organelles within tumor cells to BNCT lays the foundation for significantly improving the efficacy of BNCT in killing tumor cells.