Andrei V. Kabashin

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.

Plasmonic nanoparticles (NP) possess great potential in photothermal therapy and diagnostics. However, novel NP require a detailed examination for potential toxicity and peculiarities of interaction with cells. Red blood cells (RBC) are important for NP distribution and the development of hybrid RBC-NP delivery systems. This research explored RBC alterations induced by noble (Au and Ag) and nitride-based (TiN and ZrN) laser-synthesized plasmonic NP. Optical tweezers and conventional microscopy modalities indicated the effects arising at non-hemolytic levels, such as RBC poikilocytosis, and alterations in RBC microrheological parameters, elasticity and intercellular interactions. Aggregation and deformability significantly decreased for echinocytes independently of NP type, while for intact RBC, all NP except Ag NP increased the interaction forces but had no effect on RBC deformability. RBC poikilocytosis promoted by NP at concentration 50 μg mL−1 was more pronounced for Au and Ag NP, compared to TiN and ZrN NP. Nitride-based NP demonstrated better biocompatibility towards RBC and higher photothermal efficiency than their noble metal counterparts.