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Insights into the Structure of Ultrasmall Fluorescent Core-Shell Silica Nanoparticles
Dong June Jang1, Rachael S Skye1, Thomas C Gardinier1
1Department of Materials Science and Engineering, Cornell University, Ithaca, New York 14853, United States.
ACS Nano
|April 10, 2026
Summary
Ultrasmall silica core nanoparticles, approved for clinical trials, surprisingly form a stable pentagonal bipyramidal structure. This discovery explains their successful scale-up and potential therapeutic applications in oncology.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Ultrasmall fluorescent core-shell nanoparticles with silica cores and poly(ethylene glycol) shells are FDA-approved for clinical trials.
- These hybrid nanoparticles are among the few inorganic nanoparticles translated for human safety, diagnostic, and therapeutic use.
- The precise structure of their 3-4 nm silica cores remains largely unknown.
Purpose of the Study:
- To elucidate the exact core structure of ultrasmall silica nanoparticles.
- To understand the formation mechanism and stability of these nanoparticles.
- To correlate structural findings with synthesis scale-up and therapeutic potential.
Main Methods:
- Characterization using reverse-phase high-performance liquid chromatography.
- High-resolution imaging via cryogenic transmission electron microscopy.
- Computational analysis using coarse-grained simulations.
Main Results:
- Discovery of a well-defined pentagonal bipyramidal structure formed by seven primary silica nanoparticles.
- Identification of magic-size cluster formation and unusual stability.
- Rationalization of successful synthesis scale-up from 1 mL to 50 L.
Conclusions:
- The pentagonal bipyramidal core structure is key to the formation and stability of these clinically relevant nanoparticles.
- Understanding this structure provides insights into their self-therapeutic properties via ferroptosis in oncology.
- Chromatographic separation methods promise improved control over nanoparticle size distribution.

