A pH-responsive biomimetic drug delivery nanosystem for targeted chemo-photothermal therapy of tumors

Smart drug delivery nanosystem is significant for tumor treatments due to its possibility of temporally, spatially, and dose-controlled release. However, the therapeutic efficacy of drug delivery nanosystem is often compromised in cancer treatment as the enrichment of therapeutic agents in the reticuloendothelial system. Herein, doxorubicin (DOX) loaded biomimetic drug delivery nanosystem with macrophage cell membrane (MCM) camouflaged, MnFe₂O₄-DOX-MCM nanocube (NC), is developed for cancer treatment with tumor targeting, pH-stimuli drug release, and chemo-photothermal therapeutic effects. The nanosystem shows the capability of immune escape and enhanced cellular uptake of cancer cells due to the MCM decoration. Acid-labile bond between the MnFe₂O₄ NCs and DOX remains stable at physiological condition and release drugs immediately in response to the endo-/lysosome pH stimuli. Meanwhile, the photothermal effect of the nanosystem destroys tumor tissue, which further promotes chemotherapeutic efficacy. In vivo results demonstrate the tumor homing ability and produce a notable synergistic therapeutic effect of the NCs. Thus, biomimetic pH-responsive drug delivery nanosystem, MnFe₂O₄-DOX-MCM NCs, is an effective nanoplatform, which might be potential application for cancer synergistic treatment.