Nanoplatforms Derived from Iron Dextran Combined with Ascorbic Acid for Enhanced Photothermal-Chemodynamic Therapy of Tumors

The current limitations of chemodynamic therapy (CDT) are mainly due to the lack of metal ions (Fe2+, Cu+, etc.), glutathione overexpression, and insufficient hydrogen peroxide level in the tumor microenvironment. Here, we constructed a safe and effective nanoplatform (abbreviate as MPCF, M: 4T1 cell membranes; P: polydopamine; C: calcium phosphate; F: iron dextran) for tumor CDT applications based on ascorbic acid and iron dextran, which is clinically used in the treatment of iron deficiency anemia. The MPCF was fabricated by encapsulating iron dextran nanoparticles within porous calcium phosphate nanoparticle carriers and surface modifying with polydopamine and 4T1 tumor cell membranes. The MPCF can efficiently accumulate at tumor sites and gradually degrade to release the encapsulated iron dextran nanoparticles in response to the acidic tumor microenvironment. Intraperitoneally injected ascorbic acid not only generated hydrogen peroxide at the tumor site, but also synergistically acted with endogenous glutathione to reduce trivalent iron ions in the iron dextran to divalent iron ions, leading to depletion of the excess glutathione at the tumor site and amplification of oxidative stress effects. In addition, polydopamine-mediated photothermal therapy (PTT) can further enhance the CDT effect. In vitro and in vivo experiments demonstrated that the combination therapy of CDT and PTT based on the MPCF exhibited effective tumor inhibition and good biosafety properties. Therefore, the nanoplatforms prepared with the clinical drug iron dextran provide a new idea for the design of nanoprobes of tumor therapy with clinical translational potential.