mAb 功能化仿生 MamC 介导的磁脂体作为癌症治疗的药物传递系统。
mAb-Functionalized Biomimetic MamC-Mediated-Magnetoliposomes as Drug Delivery Systems for Cancer Therapy.
机构信息
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain.
Dipartimento di Scienze della Salute, Università del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
出版信息
Int J Mol Sci. 2023 Sep 11;24(18):13958. doi: 10.3390/ijms241813958.
In cancer therapy, new therapeutic nanoformulations able to mediate targeted chemotherapy are required. Recently, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC, a magnetosome protein from Magnetococcus marinus MC-1, have proven, in vitro and in vivo, to be effective drug nanocarriers (following the application of an external gradient magnetic field) and to allow combination with hyperthermia. However, these nanoassemblies require further optimization to improve cytocompatibility, stability and active targeting ability. Herein, we describe the production of the magnetoliposomes (LP) embedding BMNPs functionalized (or not) with doxorubicin (DOXO), [LP(+/-DOXO-BMNPs)], and their surface modification with the DO-24 mAb, which targets the human Met/HGF receptor's ectodomain (overexpressed in many cancers). Nanoformulations were extensively characterized using TEM, DLS, FTIR and when tested in vitro, the lipid coating increased the colloidal stability and their biocompatibility, favoring the cellular uptake in cells overexpressing the cognate receptor. Indeed, the magnetoliposomes mAb-LP(+/-DOXO-BMNPs) exerted a specific active targeting ability by the presence of the mAb that preserved its immunocompetence. Both LP(BMNPs) and mAb-LP(BMNPs) were not toxic to cells, while +/-mAb-LP(DOXO-BMNPs) nanoformulations were indeed cytotoxic. Therefore, this study represents a proof of concept for the development of promising drug carriers for cancer therapy based on local chemotherapy directed by mAbs.
在癌症治疗中,需要新的治疗性纳米制剂来介导靶向化疗。最近,来源于海洋磁球菌 MC-1 的磁小体蛋白 MamC 介导的仿生磁性纳米颗粒 (BMNPs) 已被证明在体外和体内均为有效的药物纳米载体(在施加外部梯度磁场之后),并允许与热疗相结合。然而,这些纳米组装体需要进一步优化,以提高细胞相容性、稳定性和主动靶向能力。在此,我们描述了包埋 BMNPs 的磁脂质体 (LP) 的生产(用或不用阿霉素 (DOXO) 功能化),[LP(+/-DOXO-BMNPs)],并用靶向人 Met/HGF 受体胞外域的 DO-24 mAb 对其进行表面修饰(在许多癌症中过表达)。使用 TEM、DLS、FTIR 对纳米制剂进行了广泛的表征,并且在体外进行测试时,脂质涂层增加了胶体稳定性和生物相容性,有利于在过表达同源受体的细胞中摄取细胞。实际上,磁脂质体 mAb-LP(+/-DOXO-BMNPs) 通过存在 mAb 发挥了特异性主动靶向能力,而 mAb 保留了其免疫原性。LP(BMNPs) 和 mAb-LP(BMNPs) 对细胞均无毒性,而 +/-mAb-LP(DOXO-BMNPs) 纳米制剂确实具有细胞毒性。因此,这项研究为基于 mAb 指导的局部化疗开发用于癌症治疗的有前途的药物载体提供了概念验证。