Stawarska Agnieszka, Bamburowicz-Klimkowska Magdalena, Bystrzejewski Michał, Kasprzak Artur, Grudzinski Ireneusz P
Department of Toxicology and Food Science, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.
Department of Physical Chemistry, Faculty of Chemistry, Warsaw University, Warsaw, Poland.
Int J Nanomedicine. 2025 Apr 28;20:5475-5488. doi: 10.2147/IJN.S511286. eCollection 2025.
PURPOSE: Targeting integrin receptors for MRI represents a novel method in diagnosing glioblastoma. In the present study carbon-encapsulated iron nanoparticles to explore murine glioma tracking based upon specific direct targeting with monoclonal antibodies against the beta-3 subunit (CD61) of the integrin αVβ3 receptor are described. METHODS: The carbon arc discharge method was used to synthesize nanoparticles and amidation-type reaction were applied to attach monoclonal antibody (anti-CD61) with acidic group functionalized nanoparticles to lead two types of bioconjugates (Fe@C-CONH-anti-CD61 and Fe@C-(CH)-CONH-anti-CD61). The as-synthesized bioconjugates were tested on murine glioma cells (GL261) using MTT, LDH and calcein AM/propidium iodide assays. Relaxometry measurements were performed with a 1.5 T (63 MHz) MRI scanner using both GL261 cells and C57BL/6 mice bearing GL261 tumors. RESULTS: The results showed that Fe@C-CONH-anti-CD61 and Fe@C-(CH)-CONH-anti-CD61 nanoparticles have higher binding affinity towards GL261 cells compared to pristine nanoparticles without antibodies. Studies evidenced that the antibody-decorated nanoparticles did not produce any severe cytotoxic effects on murine glioma cells. Preclinical MRI studies demonstrated that the Fe@C-(CH)-CONH-anti-CD61 nanoparticle-based construct specifically targeted murine glioma in animals. CONCLUSION: The carbon-encapsulated iron nanoparticles functionalized with monoclonal antibodies recognizing the beta-3 subunit of the integrin αVβ3 receptor can be considered as a potential contrast agent for MRI-based tracking glioblastoma.
目的:靶向整合素受体用于磁共振成像(MRI)是诊断胶质母细胞瘤的一种新方法。在本研究中,描述了基于用抗整合素αVβ3受体β-3亚基(CD61)的单克隆抗体进行特异性直接靶向来探索小鼠胶质瘤追踪的碳包裹铁纳米颗粒。 方法:采用碳弧放电法合成纳米颗粒,并应用酰胺化反应将单克隆抗体(抗CD61)与酸性基团功能化的纳米颗粒连接,得到两种生物共轭物(Fe@C-CONH-抗CD61和Fe@C-(CH)-CONH-抗CD61)。使用MTT、乳酸脱氢酶(LDH)和钙黄绿素AM/碘化丙啶检测法,对合成的生物共轭物在小鼠胶质瘤细胞(GL261)上进行测试。使用1.5T(63MHz)MRI扫描仪,对GL261细胞和携带GL261肿瘤的C57BL/6小鼠进行弛豫测量。 结果:结果表明,与未结合抗体的原始纳米颗粒相比,Fe@C-CONH-抗CD61和Fe@C-(CH)-CONH-抗CD61纳米颗粒对GL261细胞具有更高的结合亲和力。研究证明,抗体修饰的纳米颗粒对小鼠胶质瘤细胞没有产生任何严重的细胞毒性作用。临床前MRI研究表明,基于Fe@C-(CH)-CONH-抗CD61纳米颗粒的构建体在动物体内能特异性靶向小鼠胶质瘤。 结论:用识别整合素αVβ3受体β-3亚基的单克隆抗体功能化的碳包裹铁纳米颗粒可被视为基于MRI追踪胶质母细胞瘤的潜在造影剂。
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