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Testing a Nanoparticle Reagent for Imaging Mass Cytometry.

Mahtab Abtahi¹, Ladan Gheiratmand², Anuroopa Dinesh³

¹Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.

Biomacromolecules

|August 27, 2024

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This summary is machine-generated.

New nanoparticle reporters enhance imaging mass cytometry (IMC) sensitivity for detecting rare biomarkers. Coatings using poly(sulfobetaine methacrylate)-neridronate (PSBMA-Ner) effectively reduced nonspecific binding in tissue samples.

Area of Science:

Biomedical Engineering
Analytical Chemistry
Materials Science

Background:

Mass cytometry (MC) is a powerful single-cell analysis tool.
Low-abundance biomarker detection remains a challenge for MC.
Nanoparticle (NP) reagents can improve MC sensitivity by carrying multiple heavy metal isotopes.

Purpose of the Study:

To develop novel nanoparticle (NP) reporters for imaging mass cytometry (IMC).
To enhance the sensitivity and specificity of MC analysis.
To investigate the effect of NP surface modifications on nonspecific binding (NSB).

Main Methods:

Synthesized NaYF4:Yb3+/Er3+ NPs.
Functionalized NP surfaces using a two-step ligand exchange with methoxy-PEG2K-neridronate (PEG-Ner) and/or poly(sulfobetaine methacrylate)-neridronate (PSBMA-Ner).

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Evaluated colloidal stability in PBS buffer and performed IMC measurements on tonsil and breast cancer tissues.

Main Results:

Both PEG-Ner and PSBMA-Ner coatings provided long-term colloidal stability.
PSBMA-Ner or a 1:1 mixture of PSBMA-Ner + PEG-Ner effectively suppressed NSB in tonsil tissue at 2 × 10^10 NPs/mL.
Increased NSB was observed in breast cancer tissues at NP concentrations above 2 × 10^10 NPs/mL.

Conclusions:

Surface modification of NPs with PSBMA-Ner or mixed PEG-Ner/PSBMA-Ner coatings can significantly reduce NSB in IMC.
These findings pave the way for developing NP conjugates for more sensitive and specific MC analyses.
Heterobifunctional PEGs can be utilized for creating NP-bioaffinity agent conjugates for advanced MC applications.