This study aims to propose a new treatment model for glioblastoma (GBM). The combination of chemotherapy, molecular targeted therapy and radiotherapy has been achieved in a highly simultaneous manner through the application of a safe, non-toxic, locally sustained drug-releasing composite Nanofiber mesh (NFM). The NFM consisted of biodegradable poly(ε-caprolactone) with temozolomide (TMZ) and 17-allylamino-17-demethoxygeldanamycin (17AAG), which was used in radiation treatment. TMZ and 17AAG combination showed a synergistic cytotoxicity effect in the T98G cell model. TMZ and 17AAG induced a radiation-sensitization effect, respectively. The NFM containing 17AAG or TMZ, known as 17AAG-NFM and TMZ-NFM, enabled cumulative drug release of 34.1% and 39.7% within 35 days. Moreover, 17AAG+TMZ-NFM containing both drugs revealed a synergistic effect in relation to the NFM of a single agent. When combined with radiation, 17AAG+TMZ-NFM induced in an extremely powerful cytotoxic effect. These results confirmed the application of NFM can simultaneously allow multiple treatments to T98G cells. Each modality achieved a significant synergistic effect with the other, leading to a cascading amplification of the therapeutic effect. Due to the superior advantage of sustained drug release over a long period of time, NFM has the promise of clinically addressing the challenge of high recurrence of GBM post-operatively.
Boron neutron capture therapy (BNCT) is a binary radiotherapy that is based on nuclear reactions between boron-10 and low-energy neutrons, which enables selective tumor cell killing. Although accelerator-based BNCT systems are increasingly being adopted, each platform requires independent biological validation. Here, we performed an in vitro preclinical evaluation of the linac-based iBNCT001 system employing a beryllium target in combination with the clinically approved boron drug SPM-011 (borofalan (10B)). Three complementary studies were conducted: (i) a cell-based BNCT efficacy study, (ii) a free-beam radiobiological evaluation, and (iii) a radiation leakage assessment using a human-phantom model. BNCT using iBNCT001 and SPM-011 induced clear boron concentration- and dose-dependent reductions in clonogenic survival across multiple tumor cell lines. Free-beam experiments determined a relative biological effectiveness (RBE) of 2.3 for the hydrogen dose component associated with high energy neutrons. In the phantom study, the maximum radiation leakage dose during head irradiation was 1.31 GyEq in the cervical region. Although this study is limited to in vitro biological assessments, the results provide non-clinical evidence supporting the efficacy, beam quality, and biological safety of iBNCT001 for future clinical BNCT applications.