Exploring Gallium(III) Complexes as Emerging Therapeutic Candidates for Breast Cancer

Despite the clinical success of platinum chemotherapeutics,
severe
side effects and resistance drive the search for alternative metallodrugs.
Gallium compounds are promising due to their ability to mimic iron(III)
and disrupt essential cellular processes; however, poor aqueous stability
and moderate cytotoxicity have limited their development. Herein,
we report a new family of heteroscorpionate gallium(III) salts, [Ga(κ3-NNO)2][GaCl4] (Ga1–Ga6). NMR spectroscopy and single-crystal X-ray diffraction confirmed
their molecular structures. The complexes exhibit remarkable air and
moisture stability, with tunable lipophilicity and solubility governed
by ligand electronics. Ga3 and Ga6, bearing
dimethylamino substituents, showed nanomolar cytotoxicity across breast
cancer cell lines, outperforming classical platinum drugs. The lead
compound Ga6 displayed high hydrolytic stability, selective
tumor-cell uptake, cytoplasmic localization, and significant tumor
growth inhibition in zebrafish xenografts without observable systemic
toxicity in mice, underscoring the potential of the heteroscorpionate
platform.