pH-sensitive polymeric vesicles from coassembly of amphiphilic cholate grafted poly(L-lysine) and acid-cleavable polymer-drug conjugate.
PMID 22845809 · Langmuir : the ACS journal of surfaces and colloids · 2012 · DOI 10.1021/la3015767
Authors: Lijun Zhu; Lingling Zhao; Xiaozhong Qu; Zhenzhong Yang
Abstract
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.
Antineoplastic Agents; Biological Transport; Cholates; Doxorubicin; Drug Carriers; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Intracellular Space; MCF-7 Cells; Permeability; Polyethylene Glycols; Polylysine
Cite
Lijun Zhu; Lingling Zhao; Xiaozhong Qu; Zhenzhong Yang. pH-sensitive polymeric vesicles from coassembly of amphiphilic cholate grafted poly(L-lysine) and acid-cleavable polymer-drug conjugate. Langmuir : the ACS journal of surfaces and colloids (2012). PMID 22845809. DOI 10.1021/la3015767.