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18 Cell-Penetrating Peptides: Processes and Applications
of the natural tropism of this nuclear localization signal-containing peptide), the
cytoplasm 54 or even the endoplasmic reticulum and the trans-Golgi network. 35
Whether additional motifs will allow selective accumulation within one cellular
compartment has not been demonstrated, to our knowledge.
Importantly as well, a few publications have established the possibility of achieving
Tat-mediated delivery in vivo after intraperitoneal administration. 36 Comprehensive
studies of biodistribution have not been published, but evidence for delivery of
the cargo to various tissues and for crossing the blood–brain barrier has been
provided (Schwarze et al., 36 for instance).
Although no sign of toxicity has been reported yet in ex vivo and in vivo
experiments, obviously more must be done to assess the safety of Tat-based delivery
vectors. Potential toxicity for the central nervous system and immunogenicity of Tat
conjugates must be tested before considering potential clinical applications.
A potential drawback of the strategy in some applications might be the apparent
lack of selectivity of Tat-mediated drug delivery. Whether some of these Tat-based
delivery vehicles might be equipped with cell-targeting motifs allowing their preferential
accumulation in a given tissue or cell type has still to be achieved. Likewise,
combination with polymeric or particulate material might permit a controlled-release
of Tat-conjugated drugs, but, to our knowledge, this strategy has not been investigated.
ACKNOWLEDGMENTS
Work in the authors’ laboratory is supported by the Centre National de la Recherche
Scientifique (CNRS) and by grants from l’ Agence de la Recherche sur le Cancer
(ARC) and the Ligue Nationale Française Contre le Cancer (LNFCC).
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