Covalent Attachment of Aggregation-Induced Emission Molecules to the Surface of Ultrasmall Gold Nanoparticles to Enhance Cell Penetration

Klein, Kai; Hayduk, Matthias; Kollenda, Sebastian; Schmiedtchen, Marco; Voskuhl, Jens; Epple, Matthias

doi:10.3390/molecules27061788

Cited by 5 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…64 Fluorescent dyelabeled ultrasmall nanoparticles can be easily traced into and inside cells. 65 Cell penetration of ultrasmall nanoparticles is efficient, in line with results obtained for larger nanoparticles. As with larger nanoparticles, endocytosis is the predominant uptake mechanism.…”

Section: Regulating the Interactions Of Ultrasmall Nanoparticles With...supporting

confidence: 74%

See 1 more Smart Citation

The Why and How of Ultrasmall Nanoparticles

Epple,

Rotello,

Dawson

2023

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

In this Account, we describe our research into ultrasmall nanoparticles, including their unique properties, and outline some of the new opportunities they offer. We will summarize our perspective on the current state of the field and highlight what we see as key questions that remain to be solved. First, there are several nanostructure size-scale regimes, with qualitatively distinct functional biological attributes. Broadly generalized, larger particles (e.g., larger than 300 nm) tend to be more efficiently swept away by the first line of the immune system (for example macrophages). In the "middle-sized" regime (20−300 nm), nanoparticle surfaces and shapes can be recognized by energy-dependent cellular reorganizations, then organized locally in a spatial and temporally coherent way. That energy is gated and made available by specific cellular recognition processes. The relationship between particle surface design, endogenously derived nonspecific biomolecular corona, and architectural features recognized by the cell is complex and only purposefully and very precisely designed nanoparticle architectures are able to navigate to specific targets. At sufficiently small sizes (<10 nm including the ligand shell, associated with a core diameter of a few nm at most) we enter the "quasimolecular regime" in which the endogenous biomolecular environment exchanges so rapidly with the ultrasmall particle surface that larger scale cellular and immune recognition events are often greatly simplified. As an example, ultrasmall particles can penetrate cellular and biological barriers within tissue architectures via passive diffusion, in much the same way as small molecule drugs do. An intriguing question arises: what happens at the interface of cellular recognition and ultrasmall quasi-molecular size regimes? Succinctly put, ultrasmall conjugates can evade defense mechanisms driven by larger scale cellular nanoscale recognition, enabling them to flexibly exploit molecular interaction motifs to interact with specific targets. Numerous advances in control of architecture that take advantage of these phenomena have taken place or are underway. For instance, syntheses can now be sufficiently controlled that it is possible to make nanoparticles of a few hundreds of atoms or metalloid clusters of several tens of atoms that can be characterized by single crystal X-ray structure analysis. While the synthesis of atomically precise clusters in organic solvents presents challenges, water-based syntheses of ultrasmall nanoparticles can be upscaled and lead to well-defined particle populations. The surface of ultrasmall nanoparticles can be covalently modified with a wide variety of ligands to control the interactions of these particles with biosystems, as well as drugs and fluorophores. And, in contrast to larger particles, many advanced molecular analytical and separation tools can be applied to understand their structure. For example, NMR spectroscopy allows us to obtain a detailed image of the particle surface and the attached ligands. The...

show abstract

Section: Regulating the Interactions Of Ultrasmall Nanoparticles With...supporting

confidence: 74%

“…However, this autofluorescence is less efficient than that of organic fluorophores . Fluorescent dye-labeled ultrasmall nanoparticles can be easily traced into and inside cells . Cell penetration of ultrasmall nanoparticles is efficient, in line with results obtained for larger nanoparticles.…”

Section: Introductionsupporting

confidence: 54%

The Why and How of Ultrasmall Nanoparticles

Epple,

Rotello,

Dawson

2023

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…29 Here, we demonstrate how click chemistry can be used for a covalent attachment of alkyne-terminated siRNA duplex molecules to the surface of azide-terminated ultrasmall gold nanoparticles. 46 This method permits the attachment of alkynylated compounds like uorescent dyes, 46,47 molecular tweezers, 48 or aggregation-induced emission molecules (AIE) 49 to the particle surface. Ultrasmall gold nanoparticles are taken up by endocytosis, but they appear to use different endocytosis pathways.…”

Section: Introductionmentioning

confidence: 99%

Silencing of proinflammatory NF-κB and inhibition of herpes simplex virus (HSV) replication by ultrasmall gold nanoparticles (2 nm) conjugated with small-interfering RNA

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The total number of tiopronin molecules attached to the surface of each nanoparticle was determined by NMR spectroscopy. The concentrations of the conjugated doxorubicin and AF647 were determined by UV–Vis spectroscopy, as reported earlier [ 22 ]. The gold concentration in a given dispersion of nanoparticles (AuTio, AuTio-Dox, and AuTio-Dox-AF647) was determined by AAS.…”

Section: Methodsmentioning

confidence: 99%

“…Different kinds of molecules or therapeutic drugs can be covalently attached to the surfaces of ultrasmall gold nanoparticles by click chemistry [ 18 , 19 ]. Such nanoparticles have been successfully applied as delivery systems for biomolecules [ 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier

Kostka,

Sokolova,

El-Taibany

et al. 2024

Molecules

Self Cite

View full text Add to dashboard Cite

Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood–brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function.

show abstract

Covalent Attachment of Aggregation-Induced Emission Molecules to the Surface of Ultrasmall Gold Nanoparticles to Enhance Cell Penetration

Cited by 5 publications

References 51 publications

The Why and How of Ultrasmall Nanoparticles

The Why and How of Ultrasmall Nanoparticles

Silencing of proinflammatory NF-κB and inhibition of herpes simplex virus (HSV) replication by ultrasmall gold nanoparticles (2 nm) conjugated with small-interfering RNA

The Application of Ultrasmall Gold Nanoparticles (2 nm) Functionalized with Doxorubicin in Three-Dimensional Normal and Glioblastoma Organoid Models of the Blood–Brain Barrier

Contact Info

Product

Resources

About