Au@MnSe2 Core-Shell Nanoagent Enabling Immediate Generation of Hydroxyl Radicals and Simultaneous Glutathione Deletion Free of Pre-Reaction for Chemodynamic-Photothermo-Photocatalytic Therapy with Significant Immune Response

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals ((OH)-O-center dot) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: (OH)-O-center dot generated from endogenous H2O2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn2+ in MnSe2 allows immediate generation of (OH)-O-center dot, independent of pre-reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+. The Au-MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced (OH)-O-center dot generation from endogenous H2O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (approximate to 97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents.

Automated summary

A study reports the use of Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy in combination with tetramodal imaging. The nanoagent allows immediate generation of (OH)-O-dot independent of pre-reaction and enhances (OH)-O-dot generation from endogenous H2O2 and hyperthermia. The study also demonstrates an effective immune response activation and high tumor inhibition rate.