Proton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers. Laser-synthesized B NPs were efficiently absorbed by MNNG/Hos human osteosarcoma cells and did not demonstrate any remarkable toxicity effects up to concentrations of 100 ppm, as followed from the results of the MTT and clonogenic assay tests. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell death under irradiation by a 160.5 MeV proton beam. The irradiation of MNNG/Hos cells at a dose of 3 Gy in the presence of 80 and 100 ppm of B NPs led to a 2- and 2.7-fold decrease in the number of formed cell colonies compared to control samples irradiated in the absence of NPs. The obtained data unambiguously evidenced the effect of a strong proton therapy enhancement mediated by B NPs. We also found that the proton beam irradiation of B NPs leads to the generation of reactive oxygen species (ROS), which evidences a possible involvement of the non-nuclear mechanism of cancer cell death related to oxidative stress. Offering a series of advantages, including a passive targeting option and the possibility of additional theranostic functionalities based on the intrinsic properties of B NPs (e.g., photothermal therapy or neutron boron capture therapy), the proposed concept promises a major advancement in proton beam-based cancer treatment.

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a ¹⁰B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles.

The acquisition of reliable knowledge about the mechanism of short laser pulse interactions with semiconductor materials is an important step for high-tech technologies towards the development of new electronic devices, the functionalization of material surfaces with predesigned optical properties, and the manufacturing of nanorobots (such as nanoparticles) for bio-medical applications. The laser-induced nanostructuring of semiconductors, however, is a complex phenomenon with several interplaying processes occurring on a wide spatial and temporal scale. In this work, we apply the atomistic–continuum approach for modeling the interaction of an fs-laser pulse with a semiconductor target, using monolithic crystalline silicon (c-Si) and porous silicon (Si). This model addresses the kinetics of non-equilibrium laser-induced phase transitions with atomic resolution via molecular dynamics, whereas the effect of the laser-generated free carriers (electron–hole pairs) is accounted for via the dynamics of their density and temperature. The combined model was applied to study the microscopic mechanism of phase transitions during the laser-induced melting and ablation of monolithic crystalline (c-Si) and porous Si targets in a vacuum. The melting thresholds for the monolithic and porous targets were found to be 0.32 J/cm² and 0.29 J/cm², respectively. The limited heat conduction mechanism and the absence of internal stress accumulation were found to be involved in the processes responsible for the lowering of the melting threshold in the porous target. The results of this modeling were validated by comparing the melting thresholds obtained in the simulations to the experimental values. A difference in the mechanisms of ablation of the c-Si and porous Si targets was considered. Based on the simulation results, a prediction regarding the mechanism of the laser-assisted production of Si nanoparticles with the desired properties is drawn.

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.

Proton beam therapy (PBT) is a rapidly advancing modality of hadron therapy. The primary advantage of proton therapy lies in a unique depth-dose distribution characterized by the Bragg peak, which enables a highly targeted irradiation of the area limited to the tumor, while minimizing the impact on healthy tissues. However, a broader clinical adoption of the ion beam therapy is limited by both economic and radiobiological constraints. One of the possible ways to increase the relative biological effectiveness (RBE) of proton therapy involves the use of radiosensitizers. Background/Objectives: In this work, we investigated the efficacy of using colloidal solutions of lanthanum hexaboride (LaB₆) nanoparticles (NPs) coated with polyacrylic acid (PAA) as sensitizers to increase the antitumor biological effectiveness of proton irradiation. This material has not yet been studied extensively so far, despite its promising physical and chemical properties and several reports on its biocompatibility. Methods: LaB₆ NPs were synthesized by femtosecond pulsed laser ablation, functionalized with PAA and characterized. The safety of NPs was evaluated in vitro using a Live/Dead assay on cell cultures: EMT6/P, BT-474, and in vivo in Balb/c mice after intravenous (i.v.) administration. The efficacy of binary proton therapy was evaluated in vitro on cell cultures: EMT6/P, BT-474, and in vivo in the model of human ductal carcinoma of the mammary gland BT-474 in female Nu/j mice after intratumoral (i.t.) administration at a dose of 2.0 mg/mouse and local proton irradiation (fractional exposure of 31 Gy + 15 Gy). The biodistribution of LaB₆-PAA NPs in the animal body was also evaluated. Results: Significant enhancement in cancer cell death following proton beam irradiation was demonstrated in vitro on EMT6/P, BT-474 cell lines. Although the antitumor efficacy observed in vivo was comparatively lower—likely due to the high sensitivity of the BT-474 xenografts—both proton monotherapy and binary treatment were well tolerated. Conclusions: LaB₆-PAA NPs show promise as efficient sensitizers capable of enhancing the biological efficacy of proton therapy, offering a potential path forward for improving therapeutic outcomes.

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