Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic D-alpha-Tocopherol succinate (alpha-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as alpha-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/alpha-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of alpha-TOS is I mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart switch and tumor-targeted guider, had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped alpha-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded alpha-TOS. Therefore, the HA/alpha-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency.