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ACS Sensors· 2026Q1

Probing Spatiotemporal pHi and pHe Dynamics in Tumor Spheroids during Growth and Alkaline Therapy via Surface-Enhanced Raman Spectroscopy

Chunyan An, Jinghang Sun, Xuyu Zhang, Huiwen Yang et al.

Short summary

A novel nanosensor-microsensor system using Surface-Enhanced Raman Spectroscopy (SERS) allows parallel monitoring of intracellular (pHi) and extracellular (pHe) pH in tumor spheroids, revealing distinct pH profiles across cell lines and quantifying the impact of sodium bicarbonate therapy.

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Key points

  • Developed SERS nanosensors and microsensors for parallel spatiotemporal monitoring of pHi and pHe in tumor spheroids.
  • Observed distinct pHi and pHe profiles across lung (H1975), pancreatic (SW1990), and colorectal (SW480) cancer cell lines during 7-day growth.
  • Quantified the effect of 75 mM NaHCO3 treatment: pHe increased by ~0.78 units and pHi by ~0.37 units after 24 hours.
  • The system leverages size effects for precise spatial localization of pH measurements.

AI-generated from the title and abstract; the full text is not read.

Abstract

Abstract The acidic microenvironment in solid tumors is not merely a metabolic byproduct of the Warburg effect but actively promotes disease aggressiveness and treatment failure. Tumor alkalization therapy, which aims to neutralize or alkalinize the TME, has therefore emerged as a promising adjunct to conventional cancer treatments. In this study, we fabricated both SERS nanosensors and microsensors for parallel spatiotemporal monitoring of intracellular pH (pHi) and extracellular pH (pHe) within tumor spheroids derived from three human cancer cell lines: lung adenocarcinoma (H1975), pancreatic cancer (SW1990), and colorectal cancer (SW480). Over a 7-day culture period, distinct pHi and pHe profiles were observed among the different cell types. We then examined the pH modulation elicited by administration of sodium bicarbonate (NaHCO3), a clinically employed alkaline agent. Exposure to 75 mM NaHCO3 for 24 h induced a marked elevation of pHe (∼0.78 units) and a modest increment in pHi (∼0.37 units). This integrated nanosensor-microsensor system, which leverages the size effect for precise spatial localization, offers a versatile approach for elucidating the complex interactions within the tumor microenvironment and helps optimize pH-modulating cancer therapies.

The authors' abstract, as published at the source. ACS Sensors, 2026 · DOI ↗

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BioengineeringChemical Engineering