Development of an Intracellular Nitric Oxide-Donating Cell-Penetrating Polypeptide as an Immunogenic Cell Death Inducer.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-10-21 Epub Date: 2024-10-11 DOI:10.1021/acsabm.4c00941

Naeun Kim, Susam Lee, Heewon Park, Seohyeon Kim, Yeu-Chun Kim

引用次数: 0

Abstract

Recently, nitric oxide (NO) has been shown to induce immunogenic cell death (ICD) in tumor cells through endoplasmic reticulum (ER) stress and mitochondrial outer membrane permeabilization (MOMP). However, NO is unstable, making direct delivery difficult. In this study, we developed a cell-penetrating polypeptide-based NO donor, poly(l-guanidine) (PLG). Given that the guanidine structure can be catalyzed by reactive oxygen species (ROS) to produce NO, helical PLG plays three roles: spontaneous cell penetration, intracellular ROS generation to produce NO, and induction of ICD. The results revealed that helical PLG generates NO inside the cell by self-inducible guanidine oxidation and that NO effectively elicits ICD by ER stress- and MOMP-dependent intertwined mechanisms.

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开发细胞内一氧化氮捐赠细胞穿透多肽作为免疫性细胞死亡诱导剂

最近的研究表明，一氧化氮（NO）可通过内质网（ER）应激和线粒体外膜通透性（MOMP）诱导肿瘤细胞的免疫原性细胞死亡（ICD）。然而，NO 并不稳定，因此难以直接递送。在这项研究中，我们开发了一种基于细胞穿透多肽的 NO 供体--聚（l-胍）（PLG）。鉴于胍基结构可在活性氧（ROS）催化下产生 NO，螺旋 PLG 可发挥三种作用：自发细胞穿透、细胞内 ROS 生成 NO 和诱导 ICD。研究结果表明，螺旋 PLG 通过自诱导胍氧化作用在细胞内产生 NO，NO 通过 ER 应激和 MOMP 依赖性交织机制有效诱导 ICD。

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

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.