Novel l‑Arginine/Doxorubicin-Integrated Cu(II)/Sr(II) Metal-Phosphate-Organic Framework Hybrid Nanomaterials: Fabrication, Characterization, and In Vitro Cytotoxic Activities.

Nanomaterials hold significant promise in targeted cancer therapy due to their unique physicochemical properties and functional versatility. Among these, metal-phosphate-organic frameworks (MPOFs) have emerged as particularly attractive candidates for drug delivery applications. In this study, copper-(II)- and strontium-(II)-based MPOFs were synthesized and loaded with l-arginine, doxorubicin (DOX), or both, and their cytotoxic effects were evaluated against MCF-7 and A549 cancer cell lines. The synthesized nanomaterials included l-Arg@Cu-(II)-MPOF, DOX/l-Arg@Cu-(II)-MPOF, DOX@Cu-(II)-MPOF, l-Arg@Sr-(II)-MPOF, DOX/l-Arg@Sr-(II)-MPOF, and DOX@Sr-(II)-MPOF. The synthesis was performed at different pH values (5, 7.4, 9, and 11). The Cu-(II)-based MPOFs were successfully synthesized at pH 5, 7.4, and 9, while the Sr-(II)-based MPOFs could be obtained only at pH 11. The FT-IR and X-ray diffraction spectra of the synthesized MPOFs were used to characterize their structural and chemical compositions. Field emission scanning electron microscopy (FESEM), EDX, and elemental mapping analyses were also used to identify the surface morphology and elemental makeup. The surface morphology of the Cu-(II)-MPOFs, as shown by the FESEM images, had a well-defined crystalline porous nanoflower architecture with a size between 6.3 and 18.1 μm. Interestingly, the l-Arg@Sr-(II)-MPOFs also developed a stacked porous flower-like architecture, but the inclusion of DOX interfered with this architecture such that the nanosheet-like architecture was formed. The cytotoxicity of the synthesized MPOFs was determined by MTT assays in MCF-7 and A549 cell lines with IC50 values ranging from 4.19 to 22.83 μg/mL. The highest cytotoxic activity was shown by MPOFs with DOX as the only ligand in both cell lines. Also, the DOX@Cu-(II)-MPOF prepared at pH 9 revealed maximum anticancer activity, with an IC50 of 4.73 μg/mL against MCF-7 and 4.19 μg/mL against A549 cells. Sr-(II)-based MPOFs proved to be more cytotoxic toward the A549 cell line. Specifically, the DOX@Sr-(II)-MPOF proved to be most active, with an IC50 of 5.51 μg/mL against A549 cells. These results identify the promising cytotoxicity of the prepared MPOFs and introduce their prospects as new targeted cancer therapy platforms.