Dye-doped silica nanoparticles: synthesis, surface chemistry and bioapplications

Abstract

Background: Fluorescent silica nanoparticles have been extensively utilised in a broad range of biological applications and are facilitated by their predictable, wellunderstood, flexible chemistry and apparent biocompatibility. The ability to couple various siloxane precursors with fluorescent dyes and to be subsequently incorporated into silica nanoparticles has made it possible to engineer these fluorophores-doped nanomaterials to specific optical requirements in biological experimentation. Consequently, this class of nanomaterial has been used in applications across immunodiagnostics, drug delivery and human-trial bioimaging in cancer research. Main body: This review summarises the state-of-the-art of the use of dye-doped silica nanoparticles in bioapplications and firstly accounts for the common nanoparticle synthesis methods, surface modification approaches and different bioconjugation strategies employed to generate biomolecule-coated nanoparticles. The use of dye-doped silica nanoparticles in immunoassays/biosensing, bioimaging and drug delivery is then provided and possible future directions in the field are highlighted. Other non-cancerrelated applications involving silica nanoparticles are also briefly discussed. Importantly, the impact of how the protein corona has changed our understanding of NP interactions with biological systems is described, as well as demonstrations of its capacity to be favourably manipulated. Conclusions: Dye-doped silica nanoparticles have found success in the immunodiagnostics domain and have also shown promise as bioimaging agents in human clinical trials. Their use in cancer delivery has been restricted to murine models, as has been the case for the vast majority of nanomaterials intended for cancer therapy. This is hampered by the need for more human-like disease models and the lack of standardisation towards assessing nanoparticle toxicity. However, developments in the manipulation of the protein corona have improved the understanding of fundamental bio-nano interactions, and will undoubtedly assist in the translation of silica nanoparticles for disease treatment to the clinic.

Quantifying the level of nanoparticle uptake in mammalian cells using flow cytometry

“…The mechanisms for dye-doped silica nanoparticle synthesis have been well-documented, 48,49 where silane-conjugated dye molecules are incorporated into silica nanoparticles covalently when a silica matrix is produced from the precursor, tetraethyl-orthosilicate (TEOS). Since FITC molecules are covalently incorporated into the silica matrix during synthesis, rather than being modified after nanoparticle synthesis, we anticipate that dye molecules will present both the inside and outside of nanoparticles.…”

Identification of physicochemical properties that modulate nanoparticle aggregation in blood

“…Carbon and silica nanomaterials are among the most studied inorganic materials for medical applications due to their promising properties. However, some studies have shown that they are both capable of inducing the formation of thrombi, and the relevant mechanisms of action are still under debate [9]. In fact, single-walled (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) can induce platelet activation by inducing depletion of intracellular Ca 2+ [10,11], an effect that was hypothesised to be caused by the interaction of CNTs with plasma and dense tubular system membranes likely related to the fibrous shape [12].…”

Paradigms to assess the human health risks of nano- and microplastics

“…PS particles containing one, and only one, Au-SiO 2 core which encases a dye specifically selected to align with optical readout requirements, e.g. rhodamine B, fluorescein or Cy5.5) [219][220][221].…”