Advances in strategies for treating a wide variety of diseases require an efficient delivery of the active compounds
into the cytosol of target cells. One of the challenges for the efficient intracellular delivery of therapeutic biomolecules
after their cell internalization by endocytosis is to manipulate or circumvent the non-productive trafficking
from endosomes to lysosomes, where degradation may occur. Because the nanocarriers generally cannot directly cross the
lipid bilayer of the endosomes, the pH targeting approach, which can lead to as elective disruption of the endosomal
membrane, is regarded as a promising strategy to promote a specific triggered release of active biomolecules. The combination
of the endosomal acidity with the endosomolytic capability of the nanocarrier can increase the intracellular delivery
of many drugs, genes and proteins, which, therefore, might enhance their therapeutic efficacy and, in specific cases, overcome
the multidrug resistance of many bacterial and tumor cells. Different approaches have been taken to develop pHsensitive
drug delivery devices, including the incorporation of pH-responsive polymers, peptides, surfactants and fusogenic
lipids. This review focuses on the recent progress in pH-sensitive nanocarriers and their performance as nanoscale
strategies for the intracellular drug, gene and protein delivery, with emphasis on their specificity to the acidic environment
of the endosomal compartments.
Acidic environment, cell internalization, intracellular delivery, nanocarriers, nanotechnology, pH-sensitivity.
Departament de Fisiologia, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain.