Reducing agent-triggered templated synthesis of a dynamic covalent poly(disulfide)s nanonetwork: remarkable tuning in noncovalent encapsulation stabilities and cargo release†

Abstract

We demonstrated a new methodology for the templated synthesis of a crosslinked poly(disulfide)s-based dynamic covalent nanonetwork as a highly stable potential delivery vehicle for chemotherapeutic applications. The synthesis was carried out by treatment of a nanoaggregate of a biomass-derived lipoic acid-based amphiphilic monomer with a reducing agent at room temperature in open air and aqueous medium. The hydrodynamic diameter of the naoaggregate was ∼130 nm as probed by dynamic light scattering. Control over the crosslinking density was achieved by varying the ratio of monomer : reducing agent. The crosslinking percentage varied from ∼13% to ∼100%. This provided the opportunity of fine-tuning the stability of the nanocarrier, noncovalent encapsulation stabilities and kinetics of cargo release, which are highly relevant in drug-delivery applications. For a highly crosslinked nanonetwork, in the simulated redox condition of cancer cells, ∼80% release of the guest molecule was noted from the nanonetwork in a sustained manner. Controlled depolymerization of the polymer was accomplished by use of specific mol% of the same reducing agent. Finally, the reversibility and recyclability of the poly(disulfide)s to the monomeric form was achieved by treatment of the polymer with an external thiol in the presence of an organic base.