# Single‐Cell Hyperthermia: Diamond Quantum Thermometry Reveals Thermal Control of Macrophage Polarization

## TL;DR

Researchers used nanodiamonds to control and measure temperature inside cells, showing that localized heat can change immune cell behavior.

## Contribution

A quantum-enabled nanodiamond platform enables subcellular thermal control and sensing to modulate macrophage polarization.

## Key findings

- Localized intracellular hyperthermia induces pro-inflammatory macrophage polarization.
- Quantum thermometry reveals thermal gradients as regulators of immune signaling and gene expression.
- Nanodiamonds enable precise modulation of endo-lysosomal temperatures and detection of radicals.

## Abstract

Fever elevates body temperature to enhance immune response; however, intracellular temperature can fluctuate by up to 15 °C, suggesting a previously unrecognized layer of thermal regulation. While hyperthermia has long been exploited in medicine, how localized temperature gradients influence cellular fate remains poorly understood. Here, a dual‐function nanodiamond platform is introduced that integrates optically detected magnetic resonance (ODMR) thermometry with croconium‐dye‐based photothermal heating to precisely modulate temperature within endo‐lysosomal compartments of macrophages. Controlled intracellular hyperthermia triggers oxidative stress, transcriptional reprogramming, and polarization toward a pro‐inflammatory phenotype, as confirmed by immunofluorescence, flow cytometry, and transcriptomics. These findings reveal intracellular thermal gradients as active regulators of immune signaling and gene expression. By establishing a direct subcellular thermal trigger for immune activation, independent of the canonical heat‐shock pathway. This work introduces a quantum‐enabled strategy for probing and programming cellular thermodynamics at the nanoscale.

Photothermal nanodiamonds with quantum sensing capabilities generate lysosome‐confined hyperthermia, enabling simultaneous temperature and radical detection via diamond sensing. This localized thermal and oxidative stress drives pro‐inflammatory (M1) macrophage polarization, revealing a new strategy for precision immunomodulation through subcellular control of heat and redox signaling.