Metalloporphyrin-encapsulated biodegradable nanosystems for highly efficient magnetic resonance imaging-guided sonodynamic cancer therapy

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The welldefined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpDi) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r_l = 9.43 mM^-1 s^-2) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed highperformance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.