Chenfei Wang, Wei He, Rui Guo, Chaolan Pan, Haiyang Yong, Tao Bo, Yitong Zhao, Zhili Li, Feifei Wang, Weiyi Xu, Dingjin Yao, Si Zhang*, Ming Li* and Dezhong Zhou*,
{"title":"用于皮肤基因递送的内质网靶向高支链聚（β-氨基酯","authors":"Chenfei Wang, Wei He, Rui Guo, Chaolan Pan, Haiyang Yong, Tao Bo, Yitong Zhao, Zhili Li, Feifei Wang, Weiyi Xu, Dingjin Yao, Si Zhang*, Ming Li* and Dezhong Zhou*, ","doi":"10.1021/acsmaterialslett.4c0183010.1021/acsmaterialslett.4c01830","DOIUrl":null,"url":null,"abstract":"<p >Gene therapy has emerged as a promising strategy for treating various hereditary cutaneous disorders. However, the entrapment of nucleic acids in endosomes is a significant hurdle. Here we synthesized endoplasmic reticulum (ER)-targeting highly branched poly(β-amino ester)s (ER-HPAEs) and investigated their potential for skin gene delivery. The incorporation of methyl-benzenesulfonamide (NMS) moieties endowed ER-HPAEs with a strong ER-targeting ability, allowing ER-HPAE/DNA polyplexes to bypass the conventional endosomal pathway and facilitate nuclear internalization. The optimized ER-HPAEs exhibited high transfection efficiency and biocompatibility across multiple cell types, surpassing the performance of Lipofectamine 3000 (Lipo3000). Intriguingly, the ER-HPAEs can effectively deliver plasmids to mediate high-levels of transglutaminase 1 (<i>TGM1</i>), membrane-bound transcription factor peptidase site 1 (<i>MBTPS1</i>), and collagen type VII alpha 1 chain (<i>COL7A1</i>) expression both <i>in vitro</i> and <i>in vivo</i>. This study establishes a strategy for synthesizing HPAEs with ER-targeting ability and identifies potential candidates for skin gene delivery.</p>","PeriodicalId":19,"journal":{"name":"ACS Materials Letters","volume":"6 11","pages":"5048–5057 5048–5057"},"PeriodicalIF":9.6000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Endoplasmic Reticulum-Targeting Highly Branched Poly(β-amino ester)s for Skin Gene Delivery\",\"authors\":\"Chenfei Wang, Wei He, Rui Guo, Chaolan Pan, Haiyang Yong, Tao Bo, Yitong Zhao, Zhili Li, Feifei Wang, Weiyi Xu, Dingjin Yao, Si Zhang*, Ming Li* and Dezhong Zhou*, \",\"doi\":\"10.1021/acsmaterialslett.4c0183010.1021/acsmaterialslett.4c01830\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Gene therapy has emerged as a promising strategy for treating various hereditary cutaneous disorders. However, the entrapment of nucleic acids in endosomes is a significant hurdle. Here we synthesized endoplasmic reticulum (ER)-targeting highly branched poly(β-amino ester)s (ER-HPAEs) and investigated their potential for skin gene delivery. The incorporation of methyl-benzenesulfonamide (NMS) moieties endowed ER-HPAEs with a strong ER-targeting ability, allowing ER-HPAE/DNA polyplexes to bypass the conventional endosomal pathway and facilitate nuclear internalization. The optimized ER-HPAEs exhibited high transfection efficiency and biocompatibility across multiple cell types, surpassing the performance of Lipofectamine 3000 (Lipo3000). Intriguingly, the ER-HPAEs can effectively deliver plasmids to mediate high-levels of transglutaminase 1 (<i>TGM1</i>), membrane-bound transcription factor peptidase site 1 (<i>MBTPS1</i>), and collagen type VII alpha 1 chain (<i>COL7A1</i>) expression both <i>in vitro</i> and <i>in vivo</i>. This study establishes a strategy for synthesizing HPAEs with ER-targeting ability and identifies potential candidates for skin gene delivery.</p>\",\"PeriodicalId\":19,\"journal\":{\"name\":\"ACS Materials Letters\",\"volume\":\"6 11\",\"pages\":\"5048–5057 5048–5057\"},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2024-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Materials Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsmaterialslett.4c01830\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Materials Letters","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsmaterialslett.4c01830","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Endoplasmic Reticulum-Targeting Highly Branched Poly(β-amino ester)s for Skin Gene Delivery
Gene therapy has emerged as a promising strategy for treating various hereditary cutaneous disorders. However, the entrapment of nucleic acids in endosomes is a significant hurdle. Here we synthesized endoplasmic reticulum (ER)-targeting highly branched poly(β-amino ester)s (ER-HPAEs) and investigated their potential for skin gene delivery. The incorporation of methyl-benzenesulfonamide (NMS) moieties endowed ER-HPAEs with a strong ER-targeting ability, allowing ER-HPAE/DNA polyplexes to bypass the conventional endosomal pathway and facilitate nuclear internalization. The optimized ER-HPAEs exhibited high transfection efficiency and biocompatibility across multiple cell types, surpassing the performance of Lipofectamine 3000 (Lipo3000). Intriguingly, the ER-HPAEs can effectively deliver plasmids to mediate high-levels of transglutaminase 1 (TGM1), membrane-bound transcription factor peptidase site 1 (MBTPS1), and collagen type VII alpha 1 chain (COL7A1) expression both in vitro and in vivo. This study establishes a strategy for synthesizing HPAEs with ER-targeting ability and identifies potential candidates for skin gene delivery.
期刊介绍：
ACS Materials Letters is a journal that publishes high-quality and urgent papers at the forefront of fundamental and applied research in the field of materials science. It aims to bridge the gap between materials and other disciplines such as chemistry, engineering, and biology. The journal encourages multidisciplinary and innovative research that addresses global challenges. Papers submitted to ACS Materials Letters should clearly demonstrate the need for rapid disclosure of key results. The journal is interested in various areas including the design, synthesis, characterization, and evaluation of emerging materials, understanding the relationships between structure, property, and performance, as well as developing materials for applications in energy, environment, biomedical, electronics, and catalysis. The journal has a 2-year impact factor of 11.4 and is dedicated to publishing transformative materials research with fast processing times. The editors and staff of ACS Materials Letters actively participate in major scientific conferences and engage closely with readers and authors. The journal also maintains an active presence on social media to provide authors with greater visibility.
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