A DNA-Programmed Potassium Ion Magnetic Resonance Sensor.

Disrupted potassium (K+) homeostasis is an early biochemical hallmark of altered membrane potential, electrolyte imbalance, and malignant transformation, yet in vivo K+ mapping remains unrealized. Optical sensors can report K+ fluctuations but lack the penetration depth required for deep-tissue imaging. Although magnetic resonance imaging (MRI) enables noninvasive, high-resolution visualization of biochemical processes, no contrast agent has achieved K+-dependent modulation of relaxivity, precluding true K+-selective MRI. Here we report a mechanistically defined K+-activated magnetic resonance sensor (KMRS) that translates G-quadruplex folding into magnetic relaxation control. KMRS links a Gd-DOTA reporter to an iron oxide (IO) quencher through a K+-selective DNA linker. In the low-K+ state, the short Gd-IO distance enforces strong dipolar coupling that suppresses spin fluctuations and minimizes longitudinal relaxivity (r1). K+ binding induces G-quadruplex formation, increases interparticle separation, restores Gd-centered rotational dynamics, and yields a pronounced enhancement in r1 value. This mechanism-driven MRI activation enables deep-tissue visualization of pathological K+ elevations, supporting early detection of malignant foci and ion-based discrimination between tumor and benign tissues. The design establishes a generalizable framework for engineering ion-responsive MRI probes.