Multifunctional Smart Yolk-Shell Nanostructure with Mesoporous MnO Shell for Enhanced Cancer Therapy.

Manganese dioxide (MnO) 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 MnO shell still remain exciting challenges. Herein, a YSN (size, ∼75 nm) containing a mesoporous MnO shell and Er-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 MnO, UCNPs, and YSNs into one system but also endows a size-controllable hollow cavity and thickness-tunable MnO 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 the TME, degradation of the mMnO shell by HO and GSH not only generates Mn for tumor-specific T-MR imaging but also releases O 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.