MnO ₂ coated nanotheranostic LDH for synergistic cascade chemo/chemodynamic cancer therapy under the guidance of MRI-targeted diagnosis

Integrating magnetic resonance imaging (MRI)-targeted diagnosis with synergistic cascade treatments, such as chemo/chemodynamic therapy (CT/CDT), is highly desired for promoting the antitumor performance; however, the rational design of such "all-in-one" nanomedicine is still in its infancy. In this report, using MnO₂ coated layered dihydroxide (LDH) as a carrier to load chemotherapy molecule 5-flurouracil (5-FU), a novel tumor microenvironment (TME) regulating nanodrug is formed: LDH/5-FU@MnO₂. Combined guidance of CT/CDT and MRI is used to realize synergistic diagnosis and enhanced anti-tumor efficacy. MnO₂ is converted into Mn²⁺ in the presence of reducing agent GSH, the in situ generated Mn²⁺, not only serves as the chemical fuel for the Fenton reaction, combining H₂O₂ depletion and ˙OH generation, but can also be used as a nuclear magnetic contrast agent for MRI. Moreover, the tumor acidic environment is able to trigger 5-FU release for initiating chemotherapy in the tumor zone. This "all-in-one" LDH/5-FU@MnO₂ nanomedicine integrating multiple treatment modalities and magnetic resonance imaging properties, causes persistent modulation of the TME and exhibits effective antitumor theranostic performance. Such a sophisticated nanomedicine design not only achieves improved CT/CDT antitumor efficiency, but also realizes the activatable magnetic resonance imaging. This strategy combines the merits of each treatment, significantly enhancing the anticancer efficacy, and is anticipated to display promising potentials in the clinical translation plans.