Functionalized Silica Nanoparticles: A Platform for Fluorescence Imaging at the Cell and Small Animal Levels

Abstract

Going in vivo, including living cells and the whole body, is very important for gaining a better understanding of the mystery of life and requires specialized imaging techniques. The diversity, composition, and temporal-spatial variation of life activities from cells to the whole body require the analysis techniques to be fast-response, noninvasive, highly sensitive, and stable, in situ and in real-time. Functionalized nanoparticle-based fluorescence imaging techniques have the potential to meet such needs through real-time and noninvasive visualization of biological events in vivo. Functionalized silica nanoparticles (SiNPs) doped with fluorescent dyes appear to be an ideal and flexible platform for developing fluorescence imaging techniques used in living cells and the whole body. We can select and incorporate different dyes inside the silica matrix either noncovalently or covalently. These form the functionalized hybrid SiNPs, which support multiplex labeling and ratiometric sensing in living systems. Since the silica matrix protects dyes from outside quenching and degrading factors, this enhances the photostability and biocompatibility of the SiNP-based probes. This makes them ideal for real-time and long-time tracking. One nanoparticle can encapsulate large numbers of dye molecules, which amplifies their optical signal and temporal-spatial resolution response. Integrating fluorescent dye-doped SiNPs with targeting ligands using various surface modification techniques can greatly improve selective recognition. Along with the endocytosis, functionalized SiNPs can be efficiently internalized into cells for noninvasive localization, assessment, and monitoring. These unique characteristics of functionalized SiNPs substantially support their applications in fluorescence imaging in vivo. In this Account, we summarize our efforts to develop functionalized dye-doped SiNPs for fluorescence imaging at the cell and small animal levels. We first discuss how to design and construct various functionalized dye-doped SiNPs. Then we describe their properties and imaging applications in cell surface receptor recognition, intracellular labeling, tracking, sensing, and controlled release. Additionally, we have demonstrated the promising application of dye-doped SiNPs as contrast imaging agents for in vivo fluorescence imaging in small animals. We expect these functionalized dye-doped SiNPs to open new opportunities for biological and medical research and applications.

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…Dye-doped SiNPs as labeling reagents have been used for imaging and detecting biological agents due to the attachment of sensitive biorecognition molecules (e.g., antibodies) to the silica surface through bioconjugation chemistries [365][366][367][368][369]. One of the greatest advantage of dye-doped SiNPs is a large number of fluorescent dye molecules encapsulated into nanoparticles, thus they provide high-quality luminescent signals and can serve as a probe with excellent photostability.…”

“…Depending on the lipophilicity of dyes they can be entrapped in an unaggregated form inside the silica pores like e.g., hydrophobic tertamethylrodamine (TMRA) linked to a hydrophilic dextran molecule (TMRA-dextran) [383]. Likewise, luminophore tris(2,2'-bipyridyl)dichlororuthenium (II) hexahydrate (Rubpy, λEx=458 nm λEm=594 nm) with methylene blue which formed a FRET pair of the model donor-aceptor [368,382] doped SiNPs. This model was used as a probe of leukemia cells [387].…”

Analysis of SiO2 nanoparticles binding proteins in rat blood and brain homogenate

“…The potential applications of nanotechnology using SiO 2 nanoparticles seem endless, with nanoparticle-based platforms now expanding in sensor and electronic devices, the food and cosmetic industries, and biomedical applications, such as drug delivery and theranostics. [7][8][9] In biomedical research, polyethyleneimine-functionalized silica particles was selected for targeting and tracking cancer cells by designing functional groups on the surface. SiO 2 nanoparticles can also be made porous, acting as nontoxic biocompatible vehicles for intracellular delivery of drugs.…”

Designed synthesis of mono-dispersed silica-based nanostructures and their applications in drug/gene delivery

“…The functionalized fluorescent nanoparticles based cell imaging and sensing techniques are of great interest because they have great potential to meet such requirements. [196][197][198][199] …”

“…210 Since then, various single-dye doped SiNPs and multiple-dye incorporated SiNPs can be generated using this method for ratiometric fluorescence probes or fluorescence resonance energy transfer (FRET) mediated large Stokes shifting fluorescence probes. 199 In addition, hybrid SiNPs doped with quantum dots have also been reported for cell imaging using the microemulsion method. 211 The coating of silica shell can reduce quantum dots' toxicity and improve its water-solubility.…”