Surface PEGylation of ZIF-8 metal-organic framework based on magnetic hydroxyapatite as a pH/magnetic targeting responsive system for anticancer drug delivery

In the present study, a zinc-based metal-organic framework/magnetic hydroxyapatite nanocomposite (Fe3O4@SiO2@HAp@ZIF-8) as new targeting drug delivery system was synthesized through the solvothermal method. Then, Fe3O4@SiO2@HAp@ZIF-8 was coated with a biocompatible layer of polyethylene glycol (PEG) (Fe3O4@SiO2@HAp@ZIF-8-PEG). The structural features of these nanocomposites were characterized using FT-IR, XRD, FE-SEM, EDX, TEM, Zeta potential, BET, and VSM analysis. The Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@SiO2@HAp@ZIF-8-PEG were applied as a carrier to encapsulate the doxorubicin (DOX) as an anticancer drug. The drug loading capacity and encapsulation efficiency of Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@-SiO2@HAp@ZIF-8-PEG were 7.6, 76.09, 9.8, and 98.12%, respectively. Moreover, a drug release study revealed that both nanocomposites were pH-dependent because of the dissolution of HAp under acidic conditions. The release kinetics of DOX from the prepared nanocomposites at pH 5 also showed that the Korsmeyer-Peppas model was the best model to describe the release mechanism of DOX from prepared systems. The in vitro cell viability results showed that synthesized systems had no significant toxicity, while DOX-loaded systems had notable and higher toxicity against A549 human lung carcinoma cell lines. The DPPH tests also showed that the prepared Fe3O4@SiO2@HAp@ZIF-8-PEG nanocomposites have excellent antioxidant activity. Therefore, all obtained re-sults clearly suggest that the as-prepared drug systems are potential and suitable candidates for targeted drug delivery applications.

Automated summary

In this study, a zinc-based metal-organic framework/magnetic hydroxyapatite nanocomposite was synthesized and coated with a biocompatible layer of polyethylene glycol as a targeting drug delivery system. The nanocomposites were characterized and utilized as carriers to encapsulate the anticancer drug doxorubicin. Both nanocomposites showed pH-dependent drug release and the Korsmeyer-Peppas model was the best fit to describe the release mechanism. The synthesized systems showed no significant toxicity and exhibited higher toxicity against lung cancer cell lines. Additionally, the nanocomposites demonstrated excellent antioxidant activity. These findings suggest that the prepared drug systems have potential for targeted drug delivery applications.