Uptake of Self-Assembling\nAmphiphilic Tryptophan-Based\nPolymer Nanoparticles in Three-Dimensional Cell Culture Models

Synthetic polymeric nanoparticles (NPs) have been proven\nto be\nessential drug delivery systems and cancer therapy tools. However,\nNPs derived from traditional linear polymers often fail to provide\nthe stability, biocompatibility, and loading efficiencies needed for\nclinical application. The present work explores strategically designed\namino acid-based NPs formed from self-assembling amphiphilic Y and\nH-shaped polymers consisting of a tryptophan-based hydrophobic segment\ncoupled to a hydrophilic block of polyethylene glycol (PEG). This\nstudy employs tryptophan due to its natural availability and abilities\nas a cancer immunotherapeutic agent. These amphiphilic polymers (<b>SM_Trp2P</b> and <b>SM_Trp4P</b>) were synthesized via a\ncombination of Steglich esterification and “click” chemistry\n(azide–alkyne cycloaddition). Their resulting NPs were characterized\nusing electron microscopy and dynamic light scattering (DLS), by which\nthe morphologies of the NPs were confirmed. Spherical NPs possessing\na tryptophan core enabled the loading of hydrophobic cargo, such as\ndrug molecules and near-infrared dyes, demonstrating the potential\nfor dual imaging and delivery applications. Cytotoxicity and spectroscopic\nanalysis of the NPs supported comparative studies between the two\npolymers and the biological relevancy of the nanomaterials. Employing\nmatrix-assisted laser desorption/ionization-imaging mass spectrometry\n(MALDI-MSI), full penetration and metabolism of irinotecan-loaded\nNPs were observed in three-dimensional cell cultures. Results indicate\nthat these strategically designed polymer frameworks and their resulting\nNPs are exceptional candidates for biomedical applications.