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

Yuanlin Wang, Xiang Sun, Yaqian Han, Kai Wang, Lixin Cheng, Ye Sun*, Flemming Besenbacher*, Miao Yu*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: OH 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, 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 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 (≈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.

OriginalsprogEngelsk
Artikelnummer2200041
TidsskriftAdvanced Healthcare Materials
Vol/bind11
Nummer14
ISSN2192-2640
DOI
StatusUdgivet - jul. 2022

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