Hierarchical Structures\nof Amino Acid Derived Polyhydroxyurethanes:\nPromising Candidates as Drug Carriers and Cell Adhesive Scaffolds

In this study, we examined the self-assembly of a series\nof biodegradable\nand biocompatible amino acid–based polyhydroxyurethanes (PHUs),\ninvestigating the structural influence of these polymers on their\nself-assembly and the resulting morphological features. The presence\nof hydrophilic and hydrophobic segments, along with carbonyl urethane,\nester, and hydroxyl groups in the PHU backbone, facilitates intermolecular\nhydrogen bonding, enabling the formation of self-assemblies with hierarchical\nnanodimensional morphologies. We determined the critical aggregation\nconcentration (CAC) and found that it largely depends on the PHU’s\nstructure. In-depth morphological studies demonstrated that the evolution\nof morphology proceeds in four steps: (1) the initial formation of\nmicelles, which act as seeds at very low concentrations, (2) the elongation\nof these micelles into nanorod or nanopalette shapes below the CAC\nrange, (3) the epitaxial growth of nanofibers at the CAC, and (4)\nthe complete formation of fibrous mats above the CAC. Additionally,\nthese hierarchical structures were utilized for the encapsulation\nand release of the drug doxorubicin (DOX). We observed that 75% of\nthe encapsulated DOX was readily released in a mildly acidic environment,\nsimilar to the physiological conditions of cancer cells. Cellular\nuptake studies confirmed the effective uptake of the drug-loaded nanoassemblies\ninto the cytoplasm of cells. Our studies also confirmed that these\nself-assembled structures can serve as effective cell adhesive scaffolds\nfor tissue engineering applications.