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 nano-systems 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 Fe 3 O 4 nanoclusters , MnO 2 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, Fe 3 O 4 cores and MnO 2 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 MnO 2 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.