A programmable matrix-robust plasmonic MetaRing biosensor for rapid SERS-based chemotherapeutic response profiling

Area of Science:

• Nanotechnology
• Biosensing
• Precision Oncology

Background:

• Assessing chemotherapeutic response is crucial for precision oncology but is challenged by tumor heterogeneity and complex biological samples.
• Current methods often require significant biological material and time, limiting rapid clinical application.

Purpose of the Study:

• To develop a programmable plasmonic biosensor (MetaRing) for rapid, label-free assessment of chemotherapeutic response.
• To demonstrate MetaRing's robustness in diverse biological matrices and its ability to identify drug sensitivity fingerprints.

Main Methods:

• Fabrication of MetaRing via dual regulation of nanoparticle concentration and evaporation temperature for deterministic nanoassembly.
• Utilizing label-free surface-enhanced Raman spectroscopy (SERS) for profiling paclitaxel (PTX) response.
• Integration with a 1D convolutional neural network for rapid classification of drug sensitivity.

Main Results:

• MetaRing demonstrated exceptional matrix robustness in various buffers and cell lysates.
• Distinct PTX-sensitivity spectral fingerprints were identified across cell lines, xenografts, and patient tissues.
• Metabolomic analysis revealed metabolic reprogramming linked to chemoresistance.
• The integrated AI model achieved >92% accuracy in classifying PTX sensitivity within 10 minutes.

Conclusions:

• MetaRing is a robust, scalable plasmonic platform for rapid phenotypic drug response profiling.
• The platform provides mechanistic insights into chemoresistance through metabolic pathway analysis.
• MetaRing shows strong translational potential for precision oncology applications.