A pH/GSH dual responsive nanoparticle with relaxivity amplification for magnetic resonance imaging and suppression of tumors and metastases

Abstract

Engineered magnetic nanoparticles combining diagnosis and therapy functions into one entity hold great potential to rejuvenate cancer treatment; however, they are still constrained by the “always on” signals and unsatisfactory therapeutic effect. Here, we report an intelligent theranostic probe based on Mn₃O₄ tetragonal bipyramids (MnTBs), which simultaneously respond to H⁺ and glutathione (GSH) with high sensitivity and quickly decompose to release Mn²⁺ in mild acidic and reductive intracellular environments. Mn²⁺ binds to the surrounding proteins to achieve a remarkable relaxivity amplification and selectively brighten the tumors. Particularly, this MR signal improvement is also effective in the detection of millimeter-sized liver metastases, with an ultrahigh contrast of 316%. Moreover, Mn²⁺ would trigger chemodynamic therapy (CDT) by exerting the Fenton-like activity to generate ˙OH from H₂O₂. Subsequently, a significant tumor suppression effect can be achieved by the GSH depletion-enhanced CDT. Besides, MnTBs manifest efficient urinary and hepatic excretions with biodegradability and minimal systemic toxicity. A pH/GSH dual responsive nanoprobe that integrates tumor diagnostic and therapeutic activities was developed to provide a new paradigm for precise diagnosis and treatment of tumors and metastases.