Dynamic-Covalent\nMesoporous Silica Nanohybrid with\npH/ROS-Responsive Drug Release for Targeted Tumor Therapy

Nanomedicine provides\npromising new methodologies for\nthe treatment\nof tumors but still faces several limitations, including poor colloidal\nstability, uncontrollable drug release, and insufficient drug targeting.\nHerein, hyaluronic acid (HA) was used to modify the surface of mesoporous\nsilica nanoparticles (MSNs) via a dynamic-covalent linker, phenylborate\nester (PBAE), termed MA. The HA modifier provided enhanced colloidal\nstability to the hybrid nanoparticles. As expected, MA exhibited an\nimproved biocompatibility and high potential for biomedical applications.\nMoreover, MA with a negatively charged surface effectively adsorbed\nthe drug Doxorubicin (DOX) inside the carriers, ensuring minimal drug\nleakage. In an acidic and reactive oxygen species (ROS)-containing\ncondition mimicking the tumor microenvironment, MA@DOX (MAD) continuously\nreleased its payloads, likely due to the cleavage of the pH/ROS-sensitive\nPBAE. Compared with free DOX, MAD had 2.2 times higher accessibility\nto tumor cells than free DOX. The favorable stability and cancer-selective\ndrug release make this nanoformulation a promising platform for potent\ncancer treatment.