硼纳米颗粒增强质子治疗癌症的研究
Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment.
发表日期:2023 Jul 26
作者:
Irina N Zavestovskaya, Anton L Popov, Danil D Kolmanovich, Gleb V Tikhonowski, Andrei I Pastukhov, Maxim S Savinov, Pavel V Shakhov, Julia S Babkova, Anton A Popov, Ivan V Zelepukin, Maria S Grigoryeva, Alexander E Shemyakov, Sergey M Klimentov, Vladimir A Ryabov, Paras N Prasad, Sergey M Deyev, Andrei V Kabashin
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
质子治疗是治疗深部和不能切除的肿瘤的一种具有潜力的放射治疗方法,其效果可以通过使用含硼物质进一步增强。在这里,我们探讨了使用元素硼(B)纳米颗粒(NPs)作为质子治疗增强的敏化剂。通过脉冲激光水中烧蚀方法制备,所用的B NPs的平均尺寸为50纳米,而随后通过聚乙二醇功能化NPs,提高了它们在缓冲液中的胶溶稳定性。激光合成的B NPs被MNNG/Hos人骨肉瘤细胞高效吸收,并且在100 ppm的浓度以下不表现出任何明显的毒性效应,这是通过MTT和克隆形成实验结果得出的。然后,我们评估了B NPs作为癌细胞死亡的敏化剂在160.5 MeV质子束照射下的效果。在存在80和100 ppm B NPs的情况下,以3 Gy剂量照射MNNG/Hos细胞导致形成的细胞克隆数量相比于在无NPs的情况下照射的对照样本减少了2倍和2.7倍。得到的数据明确证明了B NPs介导的强效质子治疗增强效应。我们还发现,质子束照射B NPs会产生活性氧自由基(ROS),这表明了与氧化应激相关的非核机制可能参与了癌细胞死亡。该概念提供了一系列优势,包括被动靶向选择和基于B NPs固有特性的额外治疗诊断功能(例如光热疗法或中子硼俘获疗法),为基于质子束的癌症治疗提供了重大进展的可能性。
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.