Celecoxib repurposing in RGD-functionalized ZIF-8 nanoparticles: An alternative strategy for breast cancer

Celecoxib (CEX), a cyclooxygenase-2 (COX-2) inhibitor with reported anticancer activity, has been explored for breast cancer therapy; however, its clinical application is hindered by poor aqueous solubility, unfavorable pharmacokinetics, and non-selective systemic distribution. Herein, we report the development of a zeolitic imidazolate framework-8 nanocarrier with RGD surface modification (CEX-RGD@nZIF-8) for targeted celecoxib delivery in breast cancer. The resulting CEX-RGD@nZIF-8 nanocarriers exhibited high encapsulation efficiency (>98%) and drug loading (∼26%) while preserving the crystalline structure and morphology of ZIF-8 following peptide functionalization. Release studies revealed minimal CEX diffusion at physiological pH (7.4) and accelerated, sustained release under mildly acidic conditions (pH 5.5), consistent with acid-responsive degradation of the ZIF-8 framework. In vitro cytotoxicity evaluation demonstrated that CEX-RGD@nZIF-8 produced significantly enhanced anticancer activity against MCF-7 breast cancer cells, achieving IC50 values of 14.6 ± 3.7 μg mL−1 (24 h) and 9.2 ± 1.3 μg mL−1 (48 h), outperforming free CEX and non-targeted formulations. High selectivity indices (SI = 3.83 at 24 h and 5.51 at 48 h) confirmed preferential cytotoxicity toward MCF-7 breast cancer cells relative to normal MRC-5 fibroblasts. This enhanced anticancer selectivity associated with RGD surface modification is potentially attributable to integrin-related cellular interactions. Overall, these findings highlight RGD-modified ZIF-8 nanoparticles as a promising nanoplatform for celecoxib delivery and breast cancer drug repurposing.

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