The generation of stabilized supramolecular nanorods from star-shaped polyglutamates

We developed a new strategy of polyglutamate nanorod preparation based on supramolecular polymers stabilized with hydrophobic drugs. Using this strategy, we prepared a family of star-shaped polyglutamates (star-PGAs) with benzenetricarboxamide (BTA)-based cores of different hydrophobicity. We then studied the self-assembly of the resulting polymers in aqueous solutions containing a physiological level of salt using fluorescence spectroscopy, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). We discovered that star-PGAs behave as classical polyelectrolytes in very dilute solutions; however, compounds with hydrophobic cores assembled into one dimensional-nanorods upon an increase in concentration due to supramolecular interactions in the core. Small hydrophobic drugs, such as doxorubicin and irinotecan, stabilized the nanorods and inhibited their disassembly at concentrations below the critical aggregation concentration (CAC). We anticipate that this simple nanorod preparation strategy from star-PGAs will enable the development of new nanomedicines with unique biodistribution profiles and biological activity.