{"title":"介孔二氧化硅纳米粒子的表面改性是在三维肿瘤微环境中引入固有癌症靶向能力的一种手段","authors":"Neeraj Prabhakar, Erica Långbacka, Ezgi Özliseli, Jesse Mattsson, Alaa Mahran, Ilida Suleymanova, Cecilia Sahlgren, Jessica M. Rosenholm, Malin Åkerfelt, Matthias Nees","doi":"10.1002/smsc.202400084","DOIUrl":null,"url":null,"abstract":"Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so-called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface-modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer-associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug-loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN-mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor-specific cytotoxic effects of a γ-secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off-target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell-specific targeting and delivery for precise and successful targeted drug delivery.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":11.1000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer-Targeting Ability in a 3D Tumor Microenvironment\",\"authors\":\"Neeraj Prabhakar, Erica Långbacka, Ezgi Özliseli, Jesse Mattsson, Alaa Mahran, Ilida Suleymanova, Cecilia Sahlgren, Jessica M. Rosenholm, Malin Åkerfelt, Matthias Nees\",\"doi\":\"10.1002/smsc.202400084\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so-called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface-modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer-associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug-loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN-mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor-specific cytotoxic effects of a γ-secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off-target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell-specific targeting and delivery for precise and successful targeted drug delivery.\",\"PeriodicalId\":29791,\"journal\":{\"name\":\"Small Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2024-07-08\",\"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.202400084\",\"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.202400084","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer-Targeting Ability in a 3D Tumor Microenvironment
Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so-called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface-modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer-associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug-loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN-mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor-specific cytotoxic effects of a γ-secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off-target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell-specific targeting and delivery for precise and successful targeted drug delivery.
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.