Glutathione depletion-mediated in situ transformation of Prussian blue nanocubes for enhanced tumor-specific imaging and photoimmunotherapy

Abstract

Tumor imaging and photoimmunotherapy hold great promise for precise and efficient tumor treatment. However, a tumor microenvironment (TME) with high redox level inhibits reactive oxygen species-mediated treatment and immune response. The traditional “always-on” phototheranostic agents have often restricted the clinical translation due to their non-specific imaging signal and phototoxicity. Herein, a novel glutathione (GSH) depletion-mediated in situ transformation strategy is proposed, and the precursors of Berlin green nanocubes can be transformed into Prussian blue nanocubes (denoted as t-PB NCs) both in tumor cells and dendritic cells (DCs), which significantly enhance the accuracy of tumor-specific three-dimensional photoacoustic imaging and tumor regional phototherapy, reducing cytotoxic effects towards healthy cells. Moreover, with GSH depletion, t-PB NCs can also enhance phototherapy to induce powerful immunogenic cell death (ICD) and promote DC maturation. Thus, this many-birds-with-one-stone GSH depletion-mediated in situ transformation strategy paves the way for tumor-specific precise photoacoustic imaging and efficient photoimmunotherapy.