HER2靶向磁性纳米载体递送中工程多肽支架的比较评估,ACS Omega

当前位置： X-MOL 学术 › ACS Omega › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

HER2靶向磁性纳米载体递送中工程多肽支架的比较评估
ACS Omega ( IF 3.7 ) Pub Date : 2021-06-10 , DOI: 10.1021/acsomega.1c01811
Victoria O Shipunova _{1,

2,

3,

4} , Olga A Kolesnikova ₁ , Polina A Kotelnikova ₁ , Vladislav D Soloviev _{1,

4} , Anton A Popov ₃ , Galina M Proshkina ₁ , Maxim P Nikitin _{1,

2,

4} , Sergey M Deyev _{1,

3}

Affiliation

靶向药物递送是现代生物医学中最有趣和最具挑战性的问题之一。对于主动靶向，通常使用全尺寸 IgG 分子 (150 kDa)。最近的研究表明，小的人工多肽支架，如 DARPins (14 kDa) 和亲和体 (8 kDa)，由于其体积小、人工性质、低免疫原性和许多其他特性，是更有前途的药物递送工具。然而，没有关于支架多肽靶向能力的比较信息，在开发药物递送系统（DDSs）时应该考虑到这一点。目前的工作是对纳米粒子结构内不同 HER2 靶向蛋白的有效性进行比较的第一项综合研究。也就是说，我们合成了三峰纳米粒子：磁性、荧光、并针对癌细胞上的 HER2 肿瘤标志物。磁性颗粒 (MP) 用 (i) 全尺寸 IgG、150 kDa、(ii) DARPin_G3、14 kDa 和 (iii) 亲和体 Z 共价修饰_HER2:342，8 kDa。我们发现与纳米颗粒表面结合的 DARPin_G3 和 Affibody Z _HER2:342分子的数量分别比曲妥珠单抗的相应值高 10 倍和 40 倍。使用磁性粒子定量 (MPQ)-细胞计数和共聚焦显微镜的方法，我们发现所有类型的磁性偶联物都特异性标记了 HER2 过表达细胞。即，我们证明颗粒与 HER2 阳性细胞的结合对于 MP*曲妥珠单抗为 1113 ± 39 fg/细胞，对于 MP*Z _HER2：342为 1431 ± 186 fg/细胞MP*DARPin_G3 为 625±21 fg/细胞，比对照 HER2 阴性细胞的相应值高 2.77、2.75 和 2.30 倍。因此，我们表明最小的 HER2 识别多肽亲和体 Z _HER2:342在纳米颗粒介导的细胞标记中的特异性和选择性方面更有效。

"点击查看英文标题和摘要"

Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting Magnetic Nanocarrier Delivery

Targeted drug delivery is one of the most intriguing and challenging issues in modern biomedicine. For active targeting, full-size IgG molecules (150 kDa) are usually used. Recent studies have revealed that small artificial polypeptide scaffolds such as DARPins (14 kDa) and affibodies (8 kDa) are much more promising tools for drug delivery due to their small size, artificial nature, low immunogenicity, and many other properties. However, there is no comparative information on the targeting abilities of scaffold polypeptides, which should be taken into account when developing drug delivery systems (DDSs). The present work is the first comprehensive study on the comparison of the effectiveness of different HER2-targeting proteins within the architecture of nanoparticles. Namely, we synthesized trimodal nanoparticles: magnetic, fluorescent, and directed toward HER2 oncomarker on cancer cells. The magnetic particles (MPs) were covalently modified with (i) full-size IgG, 150 kDa, (ii) DARPin_G3, 14 kDa, and (iii) affibody Z_HER2:342, 8 kDa. We showed that the number of DARPin_G3 and affibody Z_HER2:342 molecules conjugated to the nanoparticle surface are 10 and 40 times higher, respectively, than the corresponding value for trastuzumab. Using the methods of magnetic particle quantification (MPQ)-cytometry and confocal microscopy, we showed that all types of the obtained magnetic conjugates specifically labeled HER2-overexpressing cells. Namely, we demonstrated that particle binding to HER2-positive cells is 1113 ± 39 fg/cell for MP*trastuzumab, 1431 ± 186 fg/cell for MP*Z_HER2:342, and 625±21 fg/cell for MP*DARPin_G3, which are 2.77, 2.75, and 2.30 times higher than the corresponding values for control HER2-negative cells. Thus, we showed that the smallest HER2-recognizing polypeptide affibody Z_HER2:342 is more effective in terms of specificity and selectivity in nanoparticle-mediated cell labeling.

更新日期：2021-06-22

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南