# Development of Biological-Window-Active Au Open-Shell Nanoparticles with High-Sensitivity Surface-Enhanced Raman Scattering Imaging Probe Properties

**Authors:** Kosuke Sugawa, Yuka Hori, Azusa Onozato, Hikaru Naitoh, Arisa Suzuki, Tamaki Amemiya, Hironobu Tahara, Tsuyoshi Kimura, Yasuhiro Kosuge, Keiji Ohno, Takeshi Hashimoto, Takashi Hayashita, Joe Otsuki

PMC · DOI: 10.3390/nano16040271 · 2026-02-20

## TL;DR

Researchers developed biocompatible gold nanoparticles that emit strong Raman signals in the near-infrared range, suitable for cellular imaging without toxic surfactants.

## Contribution

A surfactant-free method to create gold open-shell nanoparticles with high SERS activity in the biological window is introduced.

## Key findings

- AuOSNs exhibit strong NIR LSP resonance at ~793 nm, matching the 785 nm excitation wavelength.
- PEGylated AuOSNs show negligible cytotoxicity and enable SERS imaging of HeLa cells.
- AuOSNs modified with 4-MBA achieve SERS enhancement factors of ~10^6 in aqueous dispersion.

## Abstract

The development of anisotropic gold nanostructures supporting localized surface plasmon (LSP) resonances in the near-infrared (NIR) biological window is of great interest for diagnostic and therapeutic nanotechnologies. Here, we report gold open-shell nanoparticles (AuOSNs), a symmetry-broken nanoshell architecture exhibiting strong NIR surface-enhanced Raman scattering (SERS) activity. AuOSNs were fabricated via a surfactant-free strategy combining bottom-up silica sphere assembly with a simple top-down gold deposition process, without using highly cytotoxic surfactants such as cetyltrimethylammonium bromide (CTAB). Boundary element method (BEM) simulations revealed that the asymmetric open-shell geometry induces NIR LSP resonances with pronounced electromagnetic field localization near the opening edges, depending on excitation configuration. Consistent with these predictions, extinction spectra of AuOSNs dispersed in water showed an LSP resonance peak at ~793 nm, close to the 785 nm excitation wavelength for SERS. In aqueous dispersion, AuOSNs modified with 4-mercaptobenzoic acid (4-MBA) exhibited strong SERS activity with enhancement factors of ~106. Furthermore, polyethylene glycol (PEG)-modified MBA/AuOSNs showed negligible cytotoxicity in vitro. SERS imaging confirmed that PEG/MBA/AuOSNs enable visualization of HeLa cells via characteristic MBA SERS signals. These results demonstrate that surfactant-free AuOSNs provide a biocompatible platform for NIR-excited SERS sensing and cellular imaging, highlighting their potential in plasmonic bioimaging applications.

## Linked entities

- **Chemicals:** cetyltrimethylammonium bromide (PubChem CID 5974), 4-mercaptobenzoic acid (PubChem CID 95738), polyethylene glycol (PubChem CID 9033)

## Full-text entities

- **Diseases:** injury to (MESH:D014947), cytotoxic (MESH:D064420)
- **Chemicals:** TEOS (MESH:C040733), phenol red (MESH:D010637), Au (MESH:D006046), 4-MBA (MESH:C013594), metal (MESH:D008670), D-MEM (-), PI (MESH:D011419), H2O2 (MESH:D006861), Calcein AM (MESH:C085925), penicillin (MESH:D010406), NH3 (MESH:D000641), 1-butanol (MESH:D020001), silica (MESH:D012822), EDTA (MESH:D004492), PEG (MESH:D011092), CTAB (MESH:D000077286), PEI (MESH:D011094), nitrogen (MESH:D009584), thiol (MESH:D013438), streptomycin (MESH:D013307), polymers (MESH:D011108), CO2 (MESH:D002245), L-glutamine (MESH:D005973), water (MESH:D014867), paraformaldehyde (MESH:C003043), dendrimers (MESH:D050091), silver (MESH:D012834), polydopamine (MESH:C568283), reactive oxygen species (MESH:D017382), chloride (MESH:D002712), glucose (MESH:D005947), EtOH (MESH:D000431)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943581/full.md

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Source: https://tomesphere.com/paper/PMC12943581