Construction of Hyaluronic Acid‐Covered Hierarchically Porous MIL‐nanoMOF for Loading and Controlled Release of Doxorubicin

Abstract The porous nano‐sized metal–organic framework (nanoMOF) and its proper surface modification could greatly promote the drug loading capability and introduce biocompatibility, biodegradability, and targeting functions into nano‐drug delivery systems. Herein, the HACD@ADA‐PA/MIL‐101_NH 2 (Fe)‐P nanoparticle was successfully fabricated through supramolecular and coordination interactions from three building blocks, including hierarchically porous MIL‐101_NH 2 (Fe)‐P nanoMOF, phosphite‐modified adamantane (ADA‐PA), and β‐cyclodextrin (β‐CD)‐modified hyaluronic acid (HACD). The obtained HACD@ADA‐PA/MIL‐101_NH 2 (Fe)‐P nanoparticle was nano‐sized and highly stable in physiological fluids. The porous structure of HACD@ADA‐PA/MIL‐101_NH 2 (Fe)‐P nanoparticle could effectively load the commercial chemotherapeutic drug doxorubicin (DOX) with an encapsulation rate of 41.20 % and a loading rate of 48.84 %. The obtained drug‐loaded HACD@ADA‐PA/MIL‐101_NH 2 (Fe)‐P@DOX nanoparticle was pH‐sensitive and relatively stable at neutral condition (pH 7.2) but could release DOX in a controlled way in subacid solution at pH 5.7. The simulated in vitro DOX release experiment signified that the HACD@ADA‐PA/MIL‐101_NH 2 (Fe)‐P@DOX nanoparticle could realize the controlled release of DOX in tumor issues.