Development of a Cu/ZnO@ZIF-8 nanocomposite as a pH-responsive drug delivery vehicle for the sustained release of doxorubicin in human lung cancer cell lines

Abstract

Nowadays the targeted drug release from a stable and non-toxic drug delivery vehicle is an onerous task. In this work, we developed a ZIF-8 based nanocomposite by the incorporation of copper doped zinc oxide nanoparticles onto the ZIF-8 frameworks. The formation of the composite was confirmed with the help of various spectral analyses such as FTIR, UV–visible, PXRD, XPS, TEM, SEM-EDS, TG/DTG, BET, and photoluminescent spectroscopy. The feasibility of the material as a drug delivery vehicle was analyzed by loading doxorubicin (DOX) and monitoring its release in human lung cancer cell line A549 under different pH conditions such as 1.2, 5.5, and 7.4. The release kinetics is in good agreement with the Higuchi model with a regression coefficient of 0.9999. The composite possesses a better drug loading capacity of 43.2 % and follows a sustained release kinetics at pH 5.5. The biocompatibility of the material is also noticed by monitoring the in vitro cytotoxicity and anticancer activity through MTT assay. The composite material shows a cytotoxicity of 71.99 % against human lung cancer cell line A549 and cell viability of 37 % towards the normal fibroblast cell line L929 at 100 μg/mL. The anticancer activity of the composite loaded with DOX was compared with the pure DOX. The results showed that the composite loaded with DOX shows better anticancer activity than that of pure DOX with an IC50 of 69.89 μg/mL, lower than that of pure DOX (85.52 μg/mL). The combined effect such as better drug loading, sustained and pH-responsive release and potential anticancer activity leads to the conclusion that the ZIF-8 based nanocomposite can be used as a better therapeutic agent against human lung cancer cell line A549.