Pangua Cristina, Espuelas Socorro, Simón Jon Ander, Álvarez Samuel, Martínez-Ohárriz Cristina, Collantes María, Peñuelas Iván, Calvo Alfonso, Irache Juan M
NANO-VAC Research Group, Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, Pamplona, 31008, Spain.
Institute for Health Research (IdiSNA), Pamplona, 31008, Spain.
Drug Deliv Transl Res. 2024 Oct 25. doi: 10.1007/s13346-024-01734-3.
Bevacizumab is a monoclonal antibody (mAb) that prevents the growth of new blood vessels and is currently employed in the treatment of colorectal cancer (CRC). However, like other mAb, bevacizumab shows a limited penetration in the tumors, hampering their effectiveness and inducing adverse reactions. The aim of this work was to design and evaluate albumin-based nanoparticles, coated with dextran, as carriers for bevacizumab in order to promote its accumulation in the tumor and, thus, improve its antiangiogenic activity. These nanoparticles (B-NP-DEX50) displayed a mean size of about 250 nm and a payload of about 110 µg/mg. In a CRC mice model, these nanoparticles significantly reduced tumor growth and increased tumor doubling time, tumor necrosis and apoptosis more effectively than free bevacizumab. At the end of study, bevacizumab plasma levels were higher in the free drug group, while tumor levels were higher in the B-NP-DEX50 group (2.5-time higher). In line with this, the biodistribution study revealed that nanoparticles accumulated in the tumor core, potentially improving therapeutic efficacy while reducing systemic exposure. In summary, B-NP-DEX can be an adequate alternative to improve the therapeutic efficiency of biologically active molecules, offering a more specific biodistribution to the site of action.
贝伐单抗是一种单克隆抗体(mAb),可阻止新血管的生长,目前用于治疗结直肠癌(CRC)。然而,与其他单克隆抗体一样,贝伐单抗在肿瘤中的渗透有限,这会妨碍其疗效并引发不良反应。这项工作的目的是设计并评估以白蛋白为基础、包被葡聚糖的纳米颗粒,作为贝伐单抗的载体,以促进其在肿瘤中的蓄积,从而提高其抗血管生成活性。这些纳米颗粒(B-NP-DEX50)的平均尺寸约为250纳米,载药量约为110微克/毫克。在结直肠癌小鼠模型中,与游离贝伐单抗相比,这些纳米颗粒能更有效地显著抑制肿瘤生长、延长肿瘤倍增时间、增加肿瘤坏死和细胞凋亡。在研究结束时,游离药物组的贝伐单抗血浆水平较高,而B-NP-DEX50组的肿瘤水平较高(高2.5倍)。与此一致的是,生物分布研究表明,纳米颗粒在肿瘤核心蓄积,可能在提高治疗效果的同时减少全身暴露。总之,B-NP-DEX可以作为一种合适的替代方案来提高生物活性分子的治疗效率,为作用部位提供更具特异性的生物分布。