Transcriptomic Response of U87-MG Glioblastoma Cells to BNCT: BPA vs Boron-Loaded MOF Nanocarriers

Backgrounds Boron neutron capture therapy (BNCT) is a binary radiotherapy modality that generates high-linear-energy-transfer (LET) α particles and lithium-7 nuclei via the ¹⁰B(n,α)⁷Li reaction, enabling highly localized and efficient tumor cell eradication. Despite its therapeutic potential, comprehensive transcriptome-level characterization of glioblastoma cells following BNCT remains limited, particularly regarding how distinct boron delivery systems shape cellular responses. The clinically approved agent p-boronophenylalanine (BPA) is constrained by suboptimal tumor selectivity and heterogeneous intracellular distribution. In contrast, metal-organic framework (MOF)-based nanocarriers have recently emerged as promising alternative boron delivery platforms due to their tunable architectures and enhanced intracellular retention capacity.

Methods In this pilot bulk RNA sequencing study, we profiled transcriptomic alterations in U87-MG human glioblastoma cells exposed to identical thermal neutron fluence, comparing 50 ppm boron delivered via MOF nanoparticles with conventional BPA.

Results Our comparative transcriptomic analysis revealed a more prominent perturbation profile and a more homogeneous population-wide radiation exposure in the MOF group relative to the BPA group.

Conclusion These findings indicate that MOF nanocarriers serve as promising alternatives to traditional BPA, providing a mechanistic rationale for optimizing boron delivery and enhancing BNCT efficacy in glioblastoma.