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Design and engineering of disulfide crosslinked nanocomplexes of polyamide polyelectrolytes: stability under biorelevant conditions and potent cellular internalization of entrapped model peptide.

Counter polyelectrolytes (PEs) having a degradable polyamide backbone and controlled thiolation are prepared. Their nanosized polyelectrolyte complexes (PECs) spontaneously crosslink under ambient conditions via bioreducible disulfide bonds. These PECs are regenerable after centrifugation, and resist degradation by proteases. They are stable to variations of pH and electrolyte concentration, similar to those encountered in biological milieu. However, they are unraveled in reductive conditions. These PECs act as efficient vectors for delivering entrapped cargo. They entrap with high efficiency, and controllably release, fluorescein isothiocyanate (FITC)-insulin (a model peptide) in vitro. Potent cellular internalization of FITC-insulin within human lung cancer cells with high cell viability is demonstrated.