pH-sensitive polymeric vesicles from coassembly of amphiphilic cholate grafted poly(L-lysine) and acid-cleavable polymer-drug conjugate.

Herein we report a coassembly method toward the preparation of pH-sensitive polymeric vesicular aggregates, using comb-shaped amphiphilic polymers, i.e., cholate grafted poly(L-lysine) (PLL-CA), with an amphiphilic poly(ethylene glycol)-doxorubicin conjugate (PEG-DOX). Because the drug conjugate includes a low-pH labile bond, i.e., benzoic imine, the permeability of the coassembled polymeric vesicles can be tuned by changing either the PLL-CA/PEG-DOX weight ratio or the environmental pH from 7.4 to 6.5. Furthermore, at lower pH values such as 5.0, the vesicles destabilize. The pH sensitivity leads to enhanced uptake of the vesicles by cancer cells (MCF-7) under a condition close to the extracellular environment of solid tumor (pH = 6.5) and subsequent efficient endosome escape after the endocytosis.