NiCo₂O₄ nanoparticles as chemosensitizers: enhancing doxorubicin-ınduced ıntrinsic apoptosis in A549 and MCF-7 cells.

Bimetallic spinel NiCo₂O₄ nanoparticles (NPs) were synthesized via hydrothermal methods and characterized by XRD, SEM, and EDX analyses. This study investigated their cytotoxic, synergistic, and pro-apoptotic effects-alone and in combination with doxorubicin (Dox)-in lung (A549) and breast (MCF-7) cancer cells, with the BEAS-2B normal epithelial line serving as a non-malignant control. Cytotoxicity was evaluated by WST-8 assays, and IC₅₀ values were determined through four-parameter logistic (4PL) non-linear regression. The Combination Index (CI) was computed using the Chou-Talalay method to confirm the synergistic interaction. qRT-PCR quantified CASP6, BAX, and BCL2 expression to elucidate intrinsic apoptotic activation. NiCo₂O₄ alone displayed moderate cytotoxicity (IC₅₀ ≈176 µg/mL), while Dox showed higher potency (0.089-1.48 µM). Combination treatment reduced IC₅₀ to 12.86 µg/mL in MCF-7 and 7.87 µg/mL in A549 cells, with mean CI < 1 confirming genuine synergy. CASP6 and BAX were strongly upregulated (3-fivefold) and BCL2 was suppressed (~ 0.3-fold), indicating enhanced intrinsic apoptosis. Notably, NiCo₂O₄ demonstrated preferential toxicity toward cancer cells compared with BEAS-2B controls (selectivity index ≈ 1.96). These results establish NiCo₂O₄ as a dual-function nanomaterial-both cytotoxic and chemosensitizing-capable of amplifying doxorubicin efficacy via mitochondrial and caspase-dependent pathways. Its synergistic activity and favorable selectivity highlight the translational potential of NiCo₂O₄-based nanochemosensitization strategies.