Tumor microenvironment-responsive polydopamine-based core/shell nanoplatform for synergetic theranostics

Abstract

Theranostic agents that integrate diagnostic and therapeutic modalities have drawn extensive attention due to their ability to deliver real-time imaging-guided tumor treatment. Herein, a novel core–shell polydopamine (PDA)-based theranostic agent (PDA@TA–Fe) was fabricated via a two-step strategy. Upon 808 nm and 1064 nm laser irradiation, this agent exhibited high photothermal conversion efficiencies of 29% and 41%, respectively. After endocytosis into tumor cells, the TA–Fe shell of PDA@TA–Fe gradually disintegrated in the weakly acidic tumor microenvironment (TME), and released the TA as an acidity-activated reductant that could reduce Fe³⁺ to Fe²⁺. Subsequently, the generated Fe²⁺ reacted with H₂O₂ to generate toxic hydroxyl radicals (˙OH) via the Fenton reaction, which induced the apoptosis of tumor cells and achieved the chemodynamic therapy (CDT). The heat produced by photothermal therapy (PTT) accelerated the ˙OH generation to achieve a synergetic effect of CDT/PTT. In vivo tumor-xenograft imaging and therapeutic assays demonstrated obvious contrast enhancement at the tumor site in the T₁/T₂-weighted MR imaging and efficient tumor suppression achieved after the intravenous injection of this agent because of the enhanced permeation and retention (EPR) effect. This study offered a new strategy to design an “all-in-one” nanoplatform for T₁/T₂ MR imaging-guided synergistic cancer treatment of CDT/PTT.