Jian Wang, Shensheng Zhao, Junxi Yi, Yunyan Sun, Megha Agrawal, Michael L. Oelze, King Li, Jeffrey S. Moore, Yun-Sheng Chen
{"title":"Injectable Mechanophore Nanoparticles for Deep-Tissue Mechanochemical Dynamic Therapy","authors":"Jian Wang, Shensheng Zhao, Junxi Yi, Yunyan Sun, Megha Agrawal, Michael L. Oelze, King Li, Jeffrey S. Moore, Yun-Sheng Chen","doi":"10.1021/acsnano.4c04090","DOIUrl":null,"url":null,"abstract":"Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using nonionizing light and ultrasound to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration, and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we have proposed a mechanochemical dynamic therapy (MDT) that uses free radicals generated from mechanophore-embedded polymers under mechanical stress to produce reactive oxygen species for cancer treatment. Yet, their application in vivo is constrained by the bulk form of the polymer and the need for high ultrasound intensities for activation. In this study, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core–shell structure comprising silica nanoparticles (NPs) whose interfaces are linked to polymer brushes by an azo mechanophore moiety. Upon focused ultrasound (FUS) treatment, this injectable NP generates reactive oxygen species (ROS), demonstrating promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c04090","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using nonionizing light and ultrasound to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration, and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we have proposed a mechanochemical dynamic therapy (MDT) that uses free radicals generated from mechanophore-embedded polymers under mechanical stress to produce reactive oxygen species for cancer treatment. Yet, their application in vivo is constrained by the bulk form of the polymer and the need for high ultrasound intensities for activation. In this study, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core–shell structure comprising silica nanoparticles (NPs) whose interfaces are linked to polymer brushes by an azo mechanophore moiety. Upon focused ultrasound (FUS) treatment, this injectable NP generates reactive oxygen species (ROS), demonstrating promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.