Multistage tumor microenvironment-responsive theranostic nanopeanuts: Toward multimode imaging guided chemo-photodynamic therapy

It is of great importance to develop tumor microenvironment (TME) responsive and adjustable theranostic nanosystems for specific and efficient cancer treatment. However, carrier-based nanomedicines are often inefficacious in vivo due to low drug-loading efficiency, lack of synergistic effects, poor targeting specificity and limited drug accumulation in tumor tissues. Herein, we report a new multimodal theranostic nanoplatform which is assembled from Fe3O4 nanoclusters, MnO2 nanosheets with multifunctional and cross-linked polyphosphazene. This peanut-like nanoplatform exhibited enhanced chemo/photodynamic therapy (CT/PDT) effect as well as significant tumor-targeting capacity. In addition, Fe3O4 cores and MnO2 nanoshells enables T-1/T-2 magnetic resonance imaging (MRI) of tumor tissues, while photosensitizer methylene blue (MB) allows for fluorescence imaging and PDT simultaneously. Importantly, nanopeanut agents could dual-regulate intracellular oxygen and glutathione (GSH) levels in TME by MnO2 shells, to relieve hypoxic condition and produce enough ROS to induce cell apoptosis. Our research demonstrated that the multistage TME-responsive nanoplatform is ideally suitable for tumor specific drug delivery and real-time disease tracking with enhanced theranostic properties.