The Self-Assembly, Thermoresponsive Properties, and Potential Biomedical Relevance of Proline-Tryptophan Derived...

Stimuli-responsive polymeric micelles offer promising platforms for biomedical applications, yet achieving precise control over thermoresponsive behavior and fluorescence remains a challenge. In this study, we synthesized Poly-(NB-Prol- block- Oxa-Trp) diblock copolymers via ROMP, incorporating proline (NB-Prol) for thermoresponsiveness and the inherent fluorescence of tryptophan (Oxa-Trp). Unlike conventional thermoresponsive systems, this design leverages the dual functionality of natural amino acid motifs without the need for external dyes or labels. By adjusting segment length, we achieved tunable lower critical solution temperatures (LCSTs) and fluorescence properties, which influenced micelle self-assembly and stability. Our results confirm micelle formation in a selective solvent (DMSO:H₂O), as the fluorescence intensity decreased with increasing water content. The self-assembled micelles (90-290 nm) exhibited temperature-dependent shrinkage (15-45 °C) and aggregation (50-65 °C) due to enhanced hydrophobicity. Cytotoxicity studies across multiple cell lines demonstrated biocompatibility, while preliminary doxorubicin hydrochloride (DOX·HCl) loading supported their potential in stimuli-triggered or pulsatile drug release systems. This study provides insights into optimizing polymeric micelles as intelligent nanocarriers and lays the foundation for their future biomedical integration.