Porous Molybdenum Nitride Nanosphere as Carrier-Free and Efficient Nitric Oxide Donor for Synergistic Nitric Oxide and Chemo/Sonodynamic Therapy.

Abstract

Given its abundant physiological functions, nitric oxide (NO) has attracted much attention as a cancer therapy. The sensitive release and great supply capacity are significant indicators of NO donors and their performance. Here, a transition metal nitride (TMN) MoN@PEG is adopted as an efficient NO donor. The release process starts with H⁺-triggered denitrogen owing to the high electronegativity of the N atom and weak Mo-N bond. Then, these active NH_<i>x</i> are oxidized by O₂ and other reactive oxygen species (ROS) to form NO, endowing specific release to the tumor microenvironment (TME). With a porous nanosphere structure (80 nm), MoN@PEG does not require an extra carrier for NO delivery, contributing to ultrahigh atomic utilization for outstanding release ability (94.1 ± 5.6 μM). In addition, it can also serve as a peroxidase and sonosensitizer for anticancer treatment. To further improve the charge separation, MoN-Pt@PEG was prepared to enhance the sonodynamic therapy (SDT) effect. Accordingly, ultrasound (US) further promotes NO generation due to more ROS generation, facilitating <i>in situ</i> peroxynitrite (·ONOO^-) generation with great cytotoxicity. At the same time, the nanostructure also degrades gradually, leading to high elimination (94.6%) via feces and urine within 14-day. The synergistic NO and chemo-/sono-dynamic therapy brings prominent antitumor efficiency and further activates the immune response to inhibit metastasis and recurrence. This work develops a family of NO donors that would further widen the application of NO therapy in other fields.