Potent Antineoplastic Activity against Breast Cancer in Vitro and in Vivo of a Chloro-Substituted Polyaromatic Platinum(II) Complex and Its Platinum(IV) Prodrug

Abstract This study investigates the chemotherapeutic potential of PtII5CLSS and PtIV5CLSS against breast cancer in vivo. Cell viability was assessed 72 h post-treatment, revealing potent cytotoxic activity with IC50 values of 0.447 μM for PtII5CLSS and 0.922 μM for PtIV5CLSS. Cellular uptake studies used ICP-MS to confirm active transport of both complexes into cells, showing significant accumulation in the nuclear/cytoskeletal fractions. A 28-day toxicity study in female Sprague-Dawley rats demonstrated that escalating doses up to 15 mg/kg (PtII5CLSS) and 30 mg/kg (PtIV5CLSS) caused no mortality nor adverse effects on liver and kidney function. In a chemically induced breast cancer rat model, both complexes significantly reduced tumor weight by 93–100% at doses of 1 and 5 mg/kg, with no observable nephrotoxicity or hepatotoxicity. Histopathological analysis confirmed the reduction or absence of tumors in the majority of the treated animals with PtIV5CLSS (1 mg/kg bw) being the most effective. Toxicity evaluation in sus scrofa pigs showed that PtIV5CLSS was well tolerated at both 1- and 2.5 mg/kg bw, with no mortality, behavioral changes, or signs of acute toxicity. Overall, both PtII5CLSS and PtIV5CLSS demonstrate strong antineoplastic activity against breast cancer with a favorable safety profile, supporting their potential as alternative platinum-based chemotherapeutic agents.