A. M. Alsharabasy, D. Cherukaraveedu, J. Warneke, Ziyan Warneke, J. Galán‐Mascarós, Sharon A. Glynn, Pau Farràs, Abhay Pandit
{"title":"轻松合成具有调节聚集行为和增强一氧化氮清除特性的血红素衍生物,作为乳腺癌的新疗法","authors":"A. M. Alsharabasy, D. Cherukaraveedu, J. Warneke, Ziyan Warneke, J. Galán‐Mascarós, Sharon A. Glynn, Pau Farràs, Abhay Pandit","doi":"10.1002/smsc.202400237","DOIUrl":null,"url":null,"abstract":"\nNitric oxide (•NO) plays various pathophysiological roles in breast cancer, significantly influencing the migration of tumour cells through concentration gradients. Therefore, modulating •NO levels via selective scavenging presents a promising approach to treating aggressive •NO‐dependent cancers, such as triple‐negative breast cancer (TNBC). Hemin emerges as a potential scavenger of •NO; however, its metalloporphyrin molecules tend to aggregate in physiological solutions, which limits its biomedical applications. To address this, a modification strategy is employed to minimize aggregation and protect against physiological oxidative degradation while preserving •NO‐scavenging properties. This is achieved through a simple chemical transformation that involves hemin conjugation to aromatic residues, tyrosine, and tyramine via carbodiimide reactions. These derivatives exhibit altered electronic properties and oxidation potential compared to hemin, alongside reduced aggregation tendencies and retained •NO‐binding affinity in aqueous solutions. Furthermore, depending on the type of hemin derivative, there is an associated inhibition of TNBC cell migration. These model hemin compounds demonstrate varying •NO‐binding affinities and resistance levels to oxidative degradation and aggregation, offering insights into the design of •NO‐scavenging molecules with enhanced properties for cancer treatment.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":11.1000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Facile Synthesis of Hemin Derivatives with Modulated Aggregation Behaviour and Enhanced Nitric‐Oxide Scavenging Properties as New Therapeutics for Breast Cancer\",\"authors\":\"A. M. Alsharabasy, D. Cherukaraveedu, J. Warneke, Ziyan Warneke, J. Galán‐Mascarós, Sharon A. Glynn, Pau Farràs, Abhay Pandit\",\"doi\":\"10.1002/smsc.202400237\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\nNitric oxide (•NO) plays various pathophysiological roles in breast cancer, significantly influencing the migration of tumour cells through concentration gradients. Therefore, modulating •NO levels via selective scavenging presents a promising approach to treating aggressive •NO‐dependent cancers, such as triple‐negative breast cancer (TNBC). Hemin emerges as a potential scavenger of •NO; however, its metalloporphyrin molecules tend to aggregate in physiological solutions, which limits its biomedical applications. To address this, a modification strategy is employed to minimize aggregation and protect against physiological oxidative degradation while preserving •NO‐scavenging properties. This is achieved through a simple chemical transformation that involves hemin conjugation to aromatic residues, tyrosine, and tyramine via carbodiimide reactions. These derivatives exhibit altered electronic properties and oxidation potential compared to hemin, alongside reduced aggregation tendencies and retained •NO‐binding affinity in aqueous solutions. Furthermore, depending on the type of hemin derivative, there is an associated inhibition of TNBC cell migration. These model hemin compounds demonstrate varying •NO‐binding affinities and resistance levels to oxidative degradation and aggregation, offering insights into the design of •NO‐scavenging molecules with enhanced properties for cancer treatment.\",\"PeriodicalId\":29791,\"journal\":{\"name\":\"Small Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2024-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Small Science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/smsc.202400237\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Small Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/smsc.202400237","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Facile Synthesis of Hemin Derivatives with Modulated Aggregation Behaviour and Enhanced Nitric‐Oxide Scavenging Properties as New Therapeutics for Breast Cancer
Nitric oxide (•NO) plays various pathophysiological roles in breast cancer, significantly influencing the migration of tumour cells through concentration gradients. Therefore, modulating •NO levels via selective scavenging presents a promising approach to treating aggressive •NO‐dependent cancers, such as triple‐negative breast cancer (TNBC). Hemin emerges as a potential scavenger of •NO; however, its metalloporphyrin molecules tend to aggregate in physiological solutions, which limits its biomedical applications. To address this, a modification strategy is employed to minimize aggregation and protect against physiological oxidative degradation while preserving •NO‐scavenging properties. This is achieved through a simple chemical transformation that involves hemin conjugation to aromatic residues, tyrosine, and tyramine via carbodiimide reactions. These derivatives exhibit altered electronic properties and oxidation potential compared to hemin, alongside reduced aggregation tendencies and retained •NO‐binding affinity in aqueous solutions. Furthermore, depending on the type of hemin derivative, there is an associated inhibition of TNBC cell migration. These model hemin compounds demonstrate varying •NO‐binding affinities and resistance levels to oxidative degradation and aggregation, offering insights into the design of •NO‐scavenging molecules with enhanced properties for cancer treatment.
期刊介绍:
Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.