Metal polyphenol nanocomplexes for targeting treatment of breast tumor and lung cancer

Metal polyphenol nanocomplexes (MPNs) have been extensively investigated for tumor treatment. However, the relationship between the composition of MPNs and the anti-tumor efficacy remains poorly defined. To address this issue, three MPNs were synthesized via a simple self-assembly approach using tannic acid (TA), bovine serum albumin (BSA), polyethylene glycol (PEG), and metal ions (such as Cu2+, Mn2+, and Ca2+). The resulting MPNs exhibited a hydrodynamic diameter of ~ 200 nm, negative zeta potential, and favorable colloidal stability in biological media. Under tumor-mimicking microenvironmental conditions (low pH and/or high reactive oxygen species), both metal ions and polyphenols were rapidly released. In vitro assays demonstrated that all MPNs induced concentration- and time-dependent cytotoxicity in cancer cells. Biodistribution studies using Cy5-labeled TA-Cu and TA-Mn NPs confirmed preferential tumor accumulation. These MPNs exhibit potential in vivo antitumor effects. For example, after intravenous injection of TA-Mn NPs (20 mg/kg), the tumor volume of 4T1 and Lewis lung cancer (LLC) mouse models was only 19.35% and 14.60% of the control group, respectively. Moreover, both Cu2+- and Mn2+-based MPNs extended survival in tumor-bearing mice without inducing observable systemic toxicity. In addition, no statistically significant difference in the anti-tumor efficacy was observed between Cu2+ and Mn2+-based MPNs. Collectively, this study establishes a foundational framework for the rational design of MPNs in synergistic cancer therapy, highlighting the critical role of metal ion selection in achieving potent, safe, and tunable nanotherapeutics.