Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 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.)

Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-05-16 00:00:00 , DOI: 10.1021/acs.molpharmaceut.9b00070
Coralie M. Backlund , Ladan Parhamifar ₁ , Lisa Minter , Gregory N. Tew , Thomas L. Andresen ₁

Affiliation

Delivering peptides and proteins with intracellular function represents a promising avenue for therapeutics, but remains a challenge due to the selective permeability of the plasma membrane. The successful delivery of cytosolically active proteins would enable many opportunities, including improved vaccine development through major histocompatibility complex (MHC) class I antigen display. Extended research using cell-penetrating peptides (CPPs) has aimed to facilitate intracellular delivery of exogenous proteins with some success. A new class of polymer-based mimics termed protein transduction domain mimics (PTDMs), which maintain the positive charge and amphiphilic nature displayed by many CPPs, was developed using a poly-norbornene-based backbone. Herein, we use a previously characterized PTDM to investigate delivery of the model antigen SIINFEKL into leukocytes. Peptide delivery into over 90% of CD14+ monocytes was detected in less than 15 min with nominal inflammatory cytokine response and high cell viability. The co-delivery of a TLR9 agonist and antigen using the PTDM into antigen-presenting cells in vitro showed presentation of SIINFEKL in association with MHC class I molecules, in addition to upregulation of classical differentiation markers revealing the ability of the PTDM to successfully deliver cargo intracellularly and show application in the field of immunotherapy.

中文翻译：

蛋白质转导结构域模拟物有助于快速将抗原传递到单核细胞中

传递具有细胞内功能的肽和蛋白质代表了一种有希望的治疗方法，但是由于质膜的选择性渗透性仍然是一个挑战。胞浆活性蛋白的成功递送将带来许多机会，包括通过主要组织相容性复合物（MHC）I类抗原展示来改善疫苗开发。使用细胞穿透肽（CPPs）进行的广泛研究旨在促进外源蛋白在细胞内的递送并取得了一些成功。使用基于聚降冰片烯的骨架开发了一种新型的基于聚合物的模拟物，称为蛋白质转导域模拟物（PTDM），该模拟物维持许多CPP所显示的正电荷和两亲性质。在此处，我们使用先前表征的PTDM来研究将模型抗原SIINFEKL传递到白细胞中的过程。在不到15分钟的时间内即可检测到肽传递到90％以上的CD14 +单核细胞中，并具有标称的炎症细胞因子反应和高细胞活力。使用PTDM将TLR9激动剂和抗原共同递送到体外的抗原呈递细胞中，SIINFEKL与MHC I类分子联合呈递，此外还上调了经典分化标记，从而揭示了PTDM成功递送货物的能力。并在免疫治疗领域中显示出应用。

更新日期：2019-05-16

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南