SERS detection of lung cancer-related volatiles in exhaled breath utilizing size controllable Au NC@ZIF-8 core-shell nanoparticles

The detection of volatile organic compounds (VOCs) markers in exhaled breath based on surface-enhanced Raman scattering (SERS) technology is expected to become a non-invasive diagnosis method for lung cancer patients. However, the inherently low Raman scattering efficiency of trace VOCs in exhaled breath, coupled with the inadequate stability and uniformity of conventional Raman substrates, has hampered the practical application of SERS technologies for lung cancer biomarker detection. Additionally, the development of nanomaterials that simultaneously exhibit superior electromagnetic enhancement capabilities and efficient molecular enrichment functions remains a significant challenge. Herein, we have reported a size-effect-driven strategy for constructing Au nanocube (Au NC) @ zeolite imidazolate framework-8 (ZIF-8) core-shell nanoparticles. Tunability of Au NC@ZIF-8 shell thickness from 3 nm to 40 nm was achieved through cetyltrimethylammonium bromide (CTAB) concentration gradient control (0.5–2 mL) and ice bath kinetics control. This method requires no harsh conditions, featuring simple operation, mild reaction, and short synthesis time, successfully fabricating thin ZIF-8 shell layers with controllable structural properties. This unique architecture integrates the strong localized surface plasmon resonance (LSPR) effect of Au NCs with the porous adsorption capability of ZIF-8, realizing ultrasensitive detection of benzaldehyde (BA) with a limit of detection (LOD) of 2.5 ppb. As a straightforward approach for synthesizing homogeneous and controllable core-shell SERS-active nanoparticles, this method not only offers valuable insights for the preparation of analogous core-shell materials but also provides a robust material foundation and technical support for the non-invasive screening of lung cancer.