ABSTRACT
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Membranes of the cell surface and organelles pose a serious obstacle to the uptake of
charged hydrophilic molecules inside the cells. Many pharmacological proteins or
peptides need to be delivered intracellularly to target and modulate cellular
functions at the subcellular levels. However, because the hydrophilic behavior of
such therapeutics restricts their ability to breach the cellular barrier and interact at
subcellular level, such drugs are rather delivered intracellularly by different routes of
receptor-dependent or receptor-independent endocytosis, which results in the
formation of endosomes and ends up in lysosomes. During the endocytic process,
the drug is degraded by the acidic hydrolytic enzymes present within the lysosomes.
Some of the methods applied for intracellular drug delivery include the use of
microinjection, electroporation, or pH-sensitive liposomes; however, these methods
are either invasive, damage cell membranes, or are associated with low specificity.
A promising approach that seems to be the solution to overcoming the cellular
barrier has emerged over the last decade. In this approach, certain proteins or
peptides can be tethered to the hydrophilic drug of interest and, together, the
