Preparation and characterization of enzyme-responsive zwitterionic nanoparticles for monoclonal antibody delivery

IF 2.5 4区材料科学 Q3 MATERIALS SCIENCE, MULTIDISCIPLINARY

Frontiers of Materials Science Pub Date : 2023-12-02 DOI:10.1007/s11706-023-0667-3

Changxin Hou, Huike Xing, Xubo Yuan

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Abstract

Monoclonal antibodies have been used in many diseases, but how to improve their delivery efficiency is still a key issue. As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies, in this study, zwitterionic monomers, sulfobetaine methacrylate (SBMA), and 3-[[2-(methacryloyloxy) ethyl] dimethylammonio] propionate (CBMA) were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions. The results from dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent. These nanoparticles were spherical with the sizes of (18.7±1.9) nm (SBMA nanoparticle) and (18.2±2.1) nm (CBMA nanoparticle), and the surface contained zwitterionic polymers. It was revealed that they had no cytotoxicity, could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells, and was able to effectively penetrate endothelial cells (> 2%) by transwell. Therefore, the development of this strategy has a great prospect for the delivery of monoclonal antibodies.

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用于单克隆抗体递送的酶响应两性离子纳米颗粒的制备和表征

单克隆抗体已广泛应用于多种疾病，但如何提高单克隆抗体的递送效率仍是一个关键问题。由于两性离子聚合物的修饰可以保持单克隆抗体的稳定性和生物活性，本研究以两性离子单体、甲基丙烯酸磺基甜菜碱(SBMA)和3-[[2-(甲基丙烯酰氧基)乙基]二甲基氨酰]丙酸酯(CBMA)为载体，在MMP-2酶反应肽交联剂的帮助下制备了负载单克隆抗体的两性离子纳米颗粒，这是一个在温和条件下快速合成的过程。动态光散射(DLS)、傅里叶变换红外光谱(FTIR)和透射电子显微镜(TEM)分析结果表明，以MMP-2酶反应肽为交联剂，通过原位自由基聚合成功制备了一系列两性离子纳米粒子。纳米粒子呈球形，尺寸分别为(18.7±1.9)nm (SBMA纳米粒子)和(18.2±2.1)nm (CBMA纳米粒子)，表面含有两性离子聚合物。结果表明，它们没有细胞毒性，可以通过酶释放到肿瘤微环境中，抑制肿瘤细胞的生长，并能有效穿透内皮细胞(>2%)。因此，该策略的发展对单克隆抗体的递送具有很大的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers of Materials Science MATERIALS SCIENCE, MULTIDISCIPLINARY-

CiteScore

4.20

自引率

3.70%

发文量

515

期刊介绍： Frontiers of Materials Science is a peer-reviewed international journal that publishes high quality reviews/mini-reviews, full-length research papers, and short Communications recording the latest pioneering studies on all aspects of materials science. It aims at providing a forum to promote communication and exchange between scientists in the worldwide materials science community. The subjects are seen from international and interdisciplinary perspectives covering areas including (but not limited to): Biomaterials including biomimetics and biomineralization; Nano materials; Polymers and composites; New metallic materials; Advanced ceramics; Materials modeling and computation; Frontier materials synthesis and characterization; Novel methods for materials manufacturing; Materials performance; Materials applications in energy, information and biotechnology.