Hierarchical design of intelligent α-MnO2-based theranostics nanoplatform for TME-activated drug delivery and T1-weighted MRI

Intelligent “theranostic” nanoplatforms were synthesized based on porous α-MnO2 nanostructures with various concentrations of Gd3+ doping agent (H-GdxMn1-xO2; x = 0.00–0.12 in steps 0.03). After optimization of the doping agent at x = 0.09, the surface of the nanostructures was covered with the chitosan cross-linked tripolyphosphate (Chi-TPP) to reduce the inherent toxicity of the Gd3+ ion. Then a significant amount of doxorubicin (DOX) was loaded on these porous nanoplatforms. The characteristic features of the tumor microenvironment (TME) such as low pH, high temperature, high level of glutathione (GSH), and overproduced endogenous H2O2 act as the driving force to enhance catalytic destruction of the as-synthesized nanoplatforms. Catalytic demolition of H-GdxMn1-xO2@Chit-TPP@DOX “all in one” nanoplatforms not only cause the targeted delivery of pharmaceutical cargo at TME of cancer tissue but also was used for MRI bioimaging and diagnosis of TME condition. Apart from serving as a TME-activated MRI contrast agent, as-synthesized nanoplatforms also serve as a TME-modulating agent to form molecular O2 and simultaneously attenuated tumor hypoxia. Furthermore, the future directions and challenges in the development of the H-GdxMn1-xO2@Chi-TPP@DOX “all in one” theranostic nanosystems were discussed. [Display omitted]