In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion beam therapy (CIBT), and boron neutron capture therapy (BNCT). PBT and CIBT have been reported to have excellent therapeutic results owing to the physical characteristics of their Bragg peaks. Variable drug therapies, such as chemotherapy, hormone therapy, and immunotherapy, are combined in various treatment strategies, and treatment effects have been improved. BNCT has a high dose concentration for cancer in terms of nuclear reactions with boron. BNCT is a next-generation RT that can achieve cancer cell-selective therapeutic effects, and its effectiveness strongly depends on the selective ¹⁰B accumulation in cancer cells by concomitant boron preparation. Therefore, drug delivery research, including nanoparticles, is highly desirable. In this review, we introduce both clinical and basic aspects of particle beam therapy from the perspective of multidisciplinary treatment, which is expected to expand further in the future.

The development of 4-¹⁰B-borono-2-¹⁸F-fluoro-L-phenylalanine (¹⁸FBPA) for use in positron emission tomography (PET) has contributed to the progress of boron neutron capture therapy (BNCT). ¹⁸FBPA has shown similar pharmacokinetics and distribution to 4-¹⁰B-borono-L-phenylalanine (BPA) under various conditions in many animal studies. ¹⁸FBPA PET is useful for treatment indication. A higher ¹⁸FBPA accumulation ratio of the tumor to the surrounding normal tissue (T/N ratio) indicates that a superior treatment effect is expected. In clinical settings, a T/N ratio of higher than 2.5 or 3 is often used for patient selection. Moreover, ¹⁸FBPA PET is useful for predicting the ¹⁰B concentration delivered to the tumor and surrounding normal tissues, enabling high-precision treatment planning. Precise dose prediction using ¹⁸FBPA PET data has greatly improved the treatment accuracy of BNCT. However, the methodology used for the data analysis of ¹⁸FBPA PET findings varies; thus, data should be evaluated using a consistent methodology so as to be more reliable. In addition to PET applications, the development of ¹⁸FBPA as a contrast agent for magnetic resonance imaging that combines gadolinium and ¹⁰B is also in progress.

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.

Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV µm⁻¹), neon (375 keV µm⁻¹) and argon ions (1260 keV µm⁻¹) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1–6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose.

We reports a novel thermally enhanced drug release system synthesized via a dynamic Diels-Alder (DA) reaction to develop chemotherapy for pancreatic cancer. The anticancer prodrug was designed by tethering gemcitabine (GEM) to poly(furfuryl methacrylate) (PFMA) via N-(3-maleimidopropionyloxy)succinimide as a linker by DA reaction (PFMA-L-GEM). The conversion rate of the DA reaction was found to be approximately 60% at room temperature for 120 h. The reversible deconstruction of the DA covalent bond in retro Diels-Alder (rDA) reaction was confirmed by proton nuclear magnetic resonance, and the reaction was significantly accelerated at 90 °C. A PFMA-LGEM film containing magnetic nanoparticles (MNPs) was prepared for thermally enhanced release of the drug via the rDA reaction. Drug release was initiated by heating MNPs by alternating magnetic field. This enables local heating within the film above the rDA reaction temperature while maintaining a constant surrounding medium temperature. The MNPs/PFMA-L-GEM film decreased the viability of pancreatic cancer cells by 49% over 24 h. Our results suggest that DA/rDA-based thermally enhanced drug release systems can serve as a local drug release platform and deliver the target drug within locally heated tissue, thereby improving the therapeutic efficiency and overcoming the side effects of conventional drugs used to treat pancreatic cancer. Graphical abstract