Positively Charged Lipid Nanoparticles Carry Platinum-Based Nanocages for Cancer Treatment in Living Organisms

Cationic Pt₂L₄ nanocages demonstrate 12-fold higher anticancer activity than cisplatin in vitro.

• Charge-reversed lipid nanoparticles (revLNPs) encapsulate cationic Pt₂L₄ nanocages efficiently.
• Pt₂L₄-loaded revLNPs maintain high cancer-cell uptake and cytotoxicity comparable to the free drug.
• Following intravenous administration, revLNPs show prolonged circulation and reduced leakage in vivo.
• In mice, revLNPs have a 1.7-fold longer plasma half-life than the Onpattro LNP formulation while retaining liver and spleen targeting.
• A single injection of revLNPs in zebrafish xenografts achieves tumor regression rates of 20% in PC-3M-Pro4 and 72% in MDA-MB-231 tumors.

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