A nano-integrated diagnostic and therapeutic platform with oxidation-reduction reactions in tumor microenvironments

In the present study, we developed a nano-integrated diagnostic and therapeutic platform with oxidation-reduction reactions in tumor microenvironments (TMEs). The proposed platform resolved the contradiction of particle size between the enhanced permeability and retention (EPR) effect and tumor interstitial penetration, as well as poor circulation and low drug-loading efficiency. Flower-like MnO₂ NPs were used as the core and modified with hyaluronate (HA) and H₂PtCl₆ to obtain MnO₂-HA@H₂PtCl₆ (MHP). The maximum drug-loading efficiency rate of H₂PtCl₆ reached 35% due to its chelation with HA. MHP showed satisfactory integrity and stability during circulation and can also be used as a magnetic resonance imaging (MRI) contrast agent. In addition, MHP as a radiosensitizer achieved an excellent tumor inhibition effect in combination with radiotherapy. Importantly, MHP released ultra-small nanoparticles, USNPs, (∼20 nm) through the supramolecular self-assembly abilities of Mn²⁺, HA, and H₂PtCl₆ in TMEs, leading to the increase of penetration into multicellular spheres and solid tumors (Scheme), as well as prolonging its retention in tumors.