Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy.

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.

Modeling of Short-Pulse Laser Interactions with Monolithic and Porous Silicon Targets with an Atomistic-Continuum Approach.

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.

Molecular Dynamics Modeling of Pulsed Laser Fragmentation of Solid and Porous Si Nanoparticles in Liquid Media.

The production of non-toxic and homogeneous colloidal solutions of nanoparticles (NPs) for biomedical applications is of extreme importance nowadays. Among the various methods for generation of NPs, pulsed laser ablation in liquids (PLAL) has proven itself as a powerful and efficient tool in biomedical fields, allowing chemically pure silicon nanoparticles to be obtained. For example, laser-synthesized silicon nanoparticles (Si NPs) are widely used as contrast agents for bio visualization, as effective sensitizers of radiofrequency hyperthermia for cancer theranostics, in photodynamic therapy, as carriers of therapeutic radionuclides in nuclear nanomedicine, etc. Due to a number of complex and interrelated processes involved in the laser ablation phenomenon, however, the final characteristics of the resulting particles are difficult to control, and the obtained colloidal solutions frequently have broad and multimodal size distribution. Therefore, the subsequent fragmentation of the obtained NPs in the colloidal solutions due to pulsed laser irradiation can be utilized. The resulting NPs' characteristics, however, depend on the parameters of laser irradiation as well as on the irradiated material and surrounding media properties. Thus, reliable knowledge of the mechanism of NP fragmentation is necessary for generation of a colloidal solution with NPs of predesigned properties. To investigate the mechanism of a laser-assisted NP fragmentation process, in this work, we perform a large-scale molecular dynamics (MD) modeling of FS laser interaction with colloidal solution of Si NPs. The obtained NPs are then characterized by their shape and morphological properties. The corresponding conclusion about the relative input of the properties of different laser-induced processes and materials to the mechanism of NP generation is drawn.

Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment.

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.

Strategic action or self-control? Adolescent information management and delinquency.

Recent scholarship has begun to challenge the prevailing view that children are passive recipients of parental socialization, including the common belief that parental disciplinary practices are central to explaining adolescent problem behaviors. This research shows that children exert a significant influence over parents via information management, or the degree to which children disclose information about their behavior to parents. Despite the incorporation of child information management into contemporary models of parenting, significant theoretical and empirical concerns cast doubt on its utility over classic parent-centered approaches. The current paper addresses these concerns and adjudicates between disparate definitions of adolescent information management in two ways. First, it provides a theoretically grounded definition of information management as agentic behavior. Second, it specifies a model that tests definitions of secret keeping as agentic against a non-agentic definition of secret keeping supplied by criminological theories of self-control. The model is estimated with three four-wave cross-lagged panel models, which disentangle the interrelationships between parenting, child concealment of information, and child problem behavior in a sample of high risk youth. The results offer support for a definition of concealment as strategic and self-regarding, and have implications for research on delinquency, parent-child interactions, and child agency.