PH-responsive polymeric micelles self-assembled from benzoic-imine-containing alkyl-modified PEGylated chitosan for delivery of amphiphilic drugs

Abstract

In order to efficiently promote loading efficiency and aqueous photostability of indocyanine green (ICG), an amphiphilic tricarbocyanine dye, the polysaccharide-based nanomicelles utilized as a vehicle for ICG were fabricated by self-assembly of the amphiphilic benzoic-imine-containing PEGylated chitosan/4-(dodecyloxy)benzaldehyde (DBA) conjugates in aqueous solution of pH 7.4. The resulting polymeric micelles were characterized to have a hydrophobic hybrid chitosan/DBA core surrounded by hydrophilic PEG shells. Importantly, the encapsulation of ICG into the hybrid chitosan/DBA core of polymeric micelles by the combined hydrophobic and electrostatic interactions not only promoted the ICG loading but also enhanced its aqueous photostability. With the pH of micelle suspension being reduced from 7.4 to 5.0, upon acid-triggered cleavage of benzoic-imine bonds between chitosan and DBA as well as the extending of the protonated chitosan segments from hybrid cores toward aqueous phase, the rather hydrophobic DBA-rich core was formed within micelles, thereby leading to shrinking of the polymeric micelles. The robust ICG-loaded polymeric micelles showed several superior properties including the inhibition of ICG leakage under the mimic physiological and acidic conditions, favorable biocompatibility and photo-activated hyperthermia effect. This work suggests that the pH-responsive ICG-carrying chitosan-based micelles display great potential in cancer theranostic.