Effective Reduction of Anti-PEG Antibody Recognition via PEG Copolymers with Ethyl Glycidyl Ether and Isopropyl Glycidyl Ether

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-08-12 DOI:10.1021/acs.biomac.6c01182

Verena Müller, Julian Schmidt, Rebecca Matthes, Philip Dreier, Sandra Schüttner, Matthias Bros, Holger Frey

{"title":"Effective Reduction of Anti-PEG Antibody Recognition via PEG Copolymers with Ethyl Glycidyl Ether and Isopropyl Glycidyl Ether","authors":"Verena Müller, Julian Schmidt, Rebecca Matthes, Philip Dreier, Sandra Schüttner, Matthias Bros, Holger Frey","doi":"10.1021/acs.biomac.6c01182","DOIUrl":null,"url":null,"abstract":"<div><div>Anti-PEG antibodies (APAs) lead to accelerated blood clearance of PEGylated drugs and nanocarriers. Randomized PEG (rPEG) reduces APA recognition by randomly incorporating glycidyl methyl ether in PEG. Extending this concept, statistical copolymerization of ethylene oxide with ethyl glycidyl ether (EGE) or isopropyl glycidyl ether (iPGE) was investigated. Copolymers of EO with 13–28 mol % EGE or 6–20 mol % iPGE showed low dispersity (Đ ≤ 1.09). Via online-NMR monitoring, reactivity ratios in DMSO were r EO = 1.39 and r EGE = 0.72 for P(EO-co-EGE) and r EO = 1.35 and r iPGE = 0.74 for P(EO-co-iPGE). All copolymers were soluble in PBS buffer at physiological temperatures and noncytotoxic, except for 20% iPGE content, shown by cell viability and immunostimulatory effects on murine splenocytes. All copolymers exhibit significantly reduced APA recognition (ELISA) with stronger effects for the sterically demanding iPGE. The findings highlight mP(EO-co-EGE) and mP(EO-co-iPGE) as promising PEG alternatives for nanomedicine and bioconjugation.</div></div><div>Anti-PEG antibodies (APAs) lead to accelerated blood clearance of PEGylated drugs and nanocarriers. Randomized PEG (rPEG) reduces APA recognition by randomly incorporating glycidyl methyl ether in PEG. Extending this concept, statistical copolymerization of ethylene oxide with ethyl glycidyl ether (EGE) or isopropyl glycidyl ether (iPGE) was investigated. Copolymers of EO with 13–28 mol % EGE or 6–20 mol % iPGE showed low dispersity (Đ ≤ 1.09). Via online-NMR monitoring, reactivity ratios in DMSO were r EO = 1.39 and r EGE = 0.72 for P(EO-co-EGE) and r EO = 1.35 and r iPGE = 0.74 for P(EO-co-iPGE). All copolymers were soluble in PBS buffer at physiological temperatures and noncytotoxic, except for 20% iPGE content, shown by cell viability and immunostimulatory effects on murine splenocytes. All copolymers exhibit significantly reduced APA recognition (ELISA) with stronger effects for the sterically demanding iPGE. The findings highlight mP(EO-co-EGE) and mP(EO-co-iPGE) as promising PEG alternatives for nanomedicine and bioconjugation.</div><div><div><figure><img><ol><li>Download: Download high-res image (43KB)</li><li>Download: Download full-size image</li></ol></figure></div></div><div><figure><img><ol><li>Download: Download high-res image (43KB)</li><li>Download: Download full-size image</li></ol></figure></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6165-6174"},"PeriodicalIF":5.9000,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomacromolecules","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1525779726003727","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/8/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Anti-PEG antibodies (APAs) lead to accelerated blood clearance of PEGylated drugs and nanocarriers. Randomized PEG (rPEG) reduces APA recognition by randomly incorporating glycidyl methyl ether in PEG. Extending this concept, statistical copolymerization of ethylene oxide with ethyl glycidyl ether (EGE) or isopropyl glycidyl ether (iPGE) was investigated. Copolymers of EO with 13–28 mol % EGE or 6–20 mol % iPGE showed low dispersity (Đ ≤ 1.09). Via online-NMR monitoring, reactivity ratios in DMSO were r _EO = 1.39 and r _EGE = 0.72 for P(EO-co-EGE) and r _EO = 1.35 and r _iPGE = 0.74 for P(EO-co-iPGE). All copolymers were soluble in PBS buffer at physiological temperatures and noncytotoxic, except for 20% iPGE content, shown by cell viability and immunostimulatory effects on murine splenocytes. All copolymers exhibit significantly reduced APA recognition (ELISA) with stronger effects for the sterically demanding iPGE. The findings highlight mP(EO-co-EGE) and mP(EO-co-iPGE) as promising PEG alternatives for nanomedicine and bioconjugation.

Download: Download high-res image (43KB)
Download: Download full-size image

Download: Download high-res image (43KB)
Download: Download full-size image

查看原文本刊更多论文

PEG -乙基缩水甘油醚和异丙基缩水甘油醚共聚物有效降低抗PEG抗体识别

抗聚乙二醇抗体（APAs）可加速聚乙二醇化药物和纳米载体的血液清除。随机PEG （rPEG）通过在PEG中随机加入缩水甘油酯甲基醚来降低apa识别。扩展这一概念，研究了环氧乙烷与缩水甘油酯醚（EGE）或异丙基缩水甘油酯醚（iPGE）的统计共聚。EO与13-28mol % EGE或6-20 mol % iPGE的共聚物分散性较低（Đ≤1.09）。通过在线核磁共振监测，P（EO-co-EGE）在DMSO中的反应性比rEO = 1.39, rEGE = 0.72， P（EO-co-iPGE）的反应性比rEO = 1.35, riPGE = 0.74。所有共聚物均可在生理温度下溶于PBS缓冲液中，除ipg含量为20%外，均无细胞毒性，这可以通过对小鼠脾细胞的细胞活力和免疫刺激作用来证明。所有共聚物均表现出明显降低的APArecognition (ELISA)，对空间要求较高的iPGE有更强的作用。这些发现突出了mP（EO-co-EGE）和mP（EO-co-iPGE）作为纳米医学和生物偶联的有前途的PEG替代品。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.