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

IF 11.1 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Small Science Pub Date : 2024-07-08 DOI:10.1002/smsc.202400084
Neeraj Prabhakar, Erica Långbacka, Ezgi Özliseli, Jesse Mattsson, Alaa Mahran, Ilida Suleymanova, Cecilia Sahlgren, Jessica M. Rosenholm, Malin Åkerfelt, Matthias Nees
{"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":"61 1","pages":""},"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\":\"61 1\",\"pages\":\"\"},\"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}
引用次数: 0

摘要

介孔二氧化硅纳米颗粒(MSNs)是一种很有前景的药物载体,可促进抗癌药物的靶向递送,但依靠主动靶向机制进行的效率研究仍难以实现。本研究采用体外三维共培养物(即微组织)来模拟与生理相关的肿瘤微环境(TME),以研究不含靶向配体的表面修饰MSNs对肿瘤细胞和癌症相关成纤维细胞的内化、货物递送和货物释放的影响。其中,在含有胶原蛋白的三维环境中,乙酰化的MSN最有效地定位在肿瘤细胞中,而其他MSN的定位程度较低,这很可能是由于它们仍被困在TME的细胞外基质中。疏水性模型药物负载 MSN 的共聚焦成像显示,在二维和三维共培养中,货物主要在肿瘤细胞中有效释放。与游离形式的高疏水性药物相比,MSN介导的抗癌药物在微组织中的递送显著缩小了肿瘤器官大小,并增强了γ-分泌酶抑制剂的肿瘤特异性细胞毒性作用。这种固有的靶向潜力表明,可以减少脱靶效应,提高药物疗效,从而展示了 MSN 表面修饰作为一种直接细胞特异性靶向和给药手段,实现精确和成功靶向给药的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
14.00
自引率
2.40%
发文量
0
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.
期刊最新文献
Multi-Organ Microphysiological Systems Targeting Specific Organs for Recapitulating Disease Phenotypes via Organ Crosstalk Inflammatory or Reparative? Tuning Macrophage Polarization Using Anodized Anisotropic Nanoporous Titanium Implant Surfaces Ultralow Lattice Thermal Conductivity of Zintl-Phase CaAgSb Induced by Interface and Superlattice Scattering Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons Flexible Phototransistors on Paper: Scalable Fabrication of PEDOT:PSS Devices Using a Pen Plotter
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1