Executive Summary : | Therapeutic drug monitoring (TDM) is crucial for maximizing effectiveness and minimizing toxic adverse effects in patients receiving drugs with a narrow therapeutic window, known as the therapeutic index (TI). Common drugs with low TI require close monitoring with serum blood levels, such as methotrexate, cyclosporine A, digoxin, and aminoglycoside antibiotics. Traditional methods of TDM include gas and liquid chromatography, immunoassays, and fluorescence-based rapid technologies. This proposal introduces a novel colorimetric sensor using a hybrid liposomal platform with a specific ligand to recognize the drug and multivalent aggregating linkers. The liposomes bind the target protein with lower affinity than the drug, preventing cleavage by phospholipase (PL) enzymes. The specific drug binds the protein with high affinity, making the liposome free and cleavable by the PL. Upon disruption of the bilayer, the encapsulated linkers aggregate gold nanoparticles (AuNP) featuring complementary ligands, causing a red to blue color tonality change. The liposomal platform and supramolecular chemistry for AuNP aggregation will be developed synergistically, establishing a stable, non-leaky formulation. The colorimetric platform will enable ultrasensitive detection and quantification of the drug using lateral flow assays on strips and mobile phone technology. This new methodology for TDM in biological media is faster, low-cost, and requires no special equipment. This project on label-free biosensors using novel liposomes with assembled nanoparticles could expedite research in drug discovery, toxicology, and theranostics. |