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

• Published in: Chemistry : a European journal 2021-02, Vol.27 (9), p.2987-2992
• Main Authors: Yao, Yi‐Ran, Jin, Ya‐Jun, Jia, Xin, Yang, Yang
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biodegradability; Biodegradation; Cadmium; Cell Line, Tumor; Chemistry; Construction; Controlled release; Cyclodextrin; Cyclodextrins; Delayed-Action Preparations; Doxorubicin; Doxorubicin - administration & dosage; Drug delivery; Drug delivery systems; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogen-Ion Concentration; Iron; Load distribution; Loading rate; Metal-organic frameworks; Metal-Organic Frameworks - chemical synthesis; Metal-Organic Frameworks - chemistry; Nanoparticles; Nanostructures - chemistry; pH effects; Porosity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202004335

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_NH2 (Fe)‐P nanoparticle was successfully fabricated through supramolecular and coordination interactions from three building blocks, including hierarchically porous MIL‐101_NH2 (Fe)‐P nanoMOF, phosphite‐modified adamantane (ADA‐PA), and β‐cyclodextrin (β‐CD)‐modified hyaluronic acid (HACD). The obtained HACD@ADA‐PA/MIL‐101_NH2 (Fe)‐P nanoparticle was nano‐sized and highly stable in physiological fluids. The porous structure of HACD@ADA‐PA/MIL‐101_NH2 (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_NH2 (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_NH2 (Fe)‐P@DOX nanoparticle could realize the controlled release of DOX in tumor issues. Controlled release: HACD@ADA‐PA/MIL‐101_NH2 (Fe)‐P nanoparticle was fabricated from MIL‐101_NH2 (Fe)‐P nanoMOF, phosphite‐modified adamantane (ADA‐PA), and β‐cyclodextrin (β‐CD)‐modified hyaluronic acid (HACD), by supramolecular and coordination interactions. The chemotherapeutic drug doxorubicin (DOX) could be loaded into the porous structure of the nanoparticle to obtain HACD@ADA‐PA/MIL‐101_NH2 (Fe)‐P@DOX, which was stable at pH 7.2 but could release DOX in a controlled way at pH 5.7.