Cold Plasma‐Activated Liposomes as a Strategy for Controlled Metal‐Based Drug Delivery

ABSTRACT This study introduces plasma‐triggered liposomal cargo release as a promising new approach for externally activatable drug delivery systems (DDS). The metal complex [Pt(1 S ,2 S ‐diaminocyclohexane)(4,7‐dimethoxy‐1,10‐phenanthroline)] 2+ ( 1 ) was encapsulated into L‐α‐phosphatidylcholine liposomes. Liposomal formulations of 1 were treated with a microscale atmospheric pressure plasma jet (cold atmospheric plasma, CAP), and cargo release was monitored with inductively coupled plasma optical emission spectroscopy (ICP‐OES). Moreover, the cytotoxic activity of 1 and its liposomal formulation treated with CAP for different times was analyzed via cell viability assays and calibrated to control experiments. Liposomal encapsulation enhances cytotoxicity and protects the metal complex from plasma‐induced decomposition, thereby offering a novel, enhanced DDS that overcomes the limited penetration depth of plasma‐generated short‐lived RONS as a direct antiproliferative modality.