Multifunctional Smart Yolk–Shell Nanostructure with Mesoporous MnO₂ Shell for Enhanced Cancer Therapy

Manganese dioxide (MnO₂) nanostructures have aroused great interest among analytical and biological medicine researchers as a unique type of tumor microenvironment (TME)-responsive nanomaterial. However, reliable approaches for synthesizing yolk-shell nanostructures (YSNs) with mesoporous MnO₂ shell still remain exciting challenges. Herein, a YSN (size, ∼75 nm) containing a mesoporous MnO₂ shell and Er³⁺-doped upconversion/downconversion nanoparticle (UCNP) core with a large cavity is demonstrated for the first time. This nanostructure not only integrates diverse functional components including MnO₂, UCNPs, and YSNs into one system but also endows a size-controllable hollow cavity and thickness-tunable MnO₂ layers, which can load various guest molecules like photosensitizers, methylene blue (MB), and the anticancer drugs doxorubicin (DOX). NIR-II fluorescence and photoacoustic (PA) imaging from UCNP and MB, respectively, can monitor the enrichment of the nanomaterials in the tumors for guiding chemo-photodynamic therapy (PDT) in vivo. In the TME, degradation of the mMnO₂ shell by H₂O₂ and GSH not only generates Mn²⁺ for tumor-specific T₁-MR imaging but also releases O₂ and drugs for tumor-specific treatment. The result confirmed that imaging-guided enhanced chemo-PDT combination therapy that benefited from the unique structural features of YSNs could substantially improve the therapeutic effectiveness toward malignant tumors compared to monotherapy.