使用葡聚糖包裹的白蛋白纳米粒子提高贝伐珠单抗在结直肠肿瘤小鼠模型中的疗效。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Cristina Pangua, Socorro Espuelas, Jon Ander Simón, Samuel Álvarez, Cristina Martínez-Ohárriz, María Collantes, Iván Peñuelas, Alfonso Calvo, Juan M Irache
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引用次数: 0

摘要

贝伐珠单抗是一种单克隆抗体(mAb),可阻止新生血管的生长,目前被用于治疗结直肠癌(CRC)。然而,与其他 mAb 一样,贝伐珠单抗在肿瘤中的穿透力有限,从而影响了其疗效并引发不良反应。这项工作的目的是设计和评估以白蛋白为基础、涂有葡聚糖的纳米颗粒,作为贝伐珠单抗的载体,以促进其在肿瘤内的蓄积,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,有效载荷约为 110 微克/毫克。在 CRC 小鼠模型中,这些纳米颗粒比游离贝伐珠单抗更有效地减少了肿瘤生长,延长了肿瘤倍增时间,增加了肿瘤坏死和凋亡。研究结束时,游离药物组的贝伐珠单抗血浆水平较高,而 B-NP-DEX50 组的肿瘤水平较高(高出 2.5 倍)。与此相一致,生物分布研究显示,纳米粒子在肿瘤核心积聚,可能会提高疗效,同时减少全身暴露。总之,B-NP-DEX 是提高生物活性分子治疗效率的适当替代品,它能为作用部位提供更具特异性的生物分布。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhancing bevacizumab efficacy in a colorectal tumor mice model using dextran-coated albumin nanoparticles.

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.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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