期刊
ACS APPLIED NANO MATERIALS
卷 5, 期 3, 页码 3237-3251出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsanm.1c03640
关键词
multimodal imaging; mesoporous silica nanoparticle; gold nanoparticle; stem cell tracing; reactive oxygen species
资金
- Netherlands Organization for Health Research and Development [91217058]
- Maastricht multimodal molecular imaging Institute
Stem cell (SC)-based therapies have the potential to revolutionize therapeutics by enhancing the body's natural repair processes. Researchers have developed a new nanoparticle, AuMS, which can be used to trace and monitor the biodistribution and function of SCs in vivo, with the ability for multimodal imaging and simultaneous detection of reactive oxygen species (ROS).
Stem cell (SC)-based therapies hold the potential to revolutionize therapeutics by enhancing the body's natural repair processes. Currently, there are only three SC therapies with marketing authorization within the European Union. To optimize outcomes, it is important to understand the biodistribution and behavior of transplanted SCs in vivo. A variety of imaging agents have been developed to trace SCs; however, they mostly lack the ability to simultaneously monitor the SC function and biodistribution at high resolutions. Here, we report the synthesis and application of a nanoparticle (NP) construct consisting of a gold NP core coated with rhodamine B isothiocyanate (RITC)-doped mesoporous silica (AuMS). The MS layer further contained a thiol-modified internal surface and an amine-modified external surface for dye conjugation. Highly fluorescent AuMS of three different sizes were successfully synthesized. The NPs were non-toxic and efficiently taken up by limbal epithelial SCs (LESCs). We further showed that we can functionalize AuMS with a reactive oxygen species (ROS)-sensitive fluorescent dye using two methods, loading the probe into the mesopores, with or without additional capping by a lipid bilayer, and by covalent attachment to surface and/or mesoporous-functionalized thiol groups. All four formulations displayed a ROS concentration-dependent increase in fluorescence. Further, in an ex vivo SC transplantation model, a combination of optical coherence tomography and fluorescence microscopy was used to synergistically identify AuMS-labeled LESC distribution at micrometer resolution. Our AuMS constructs allow for multimodal imaging and simultaneous ROS sensing of SCs and represent a promising tool for in vivo SC tracing.
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