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11
CONTENTS
0-8493-1141-1/02/$0.00+$1.50
© 2002 by CRC Press LLC
Toxicity and Side Effects
of Cell-Penetrating
Peptides
Margus Pooga, Anna Elmquist, and Ülo Langel
11.1 Introduction ..................................................................................................245
11.2 Toxicity Studies of CPPs .............................................................................246
11.2.1 In Vitro Toxicity ...............................................................................247
11.2.1.1 Cell Membrane Permeability............................................247
11.2.1.1.1 Exclusion of Dyes ..........................................248
11.2.1.1.2 Cytoplasmic Leakage .....................................249
11.2.1.2 Viability Assays ................................................................251
11.2.1.2.1 Enzymatic Assays...........................................251
11.2.1.2.2 Uptake Assays ................................................251
11.2.1.2.3 Ion Pump Assays ............................................252
11.2.2 CPP Toxicity In Vitro.......................................................................252
11.2.2.1 Model Amphipathic Peptides (MAPs) .............................252
11.2.2.2 Tat......................................................................................253
11.2.2.3 Penetratin ..........................................................................253
11.2.2.4 Transportan .......................................................................254
11.2.2.5 Arginine-Rich Peptides.....................................................254
11.2.2.6 Conclusions.......................................................................254
11.2.3 Side Effects of CPPs In Vitro ..........................................................255
11.2.3.1 Transportan .......................................................................255
11.2.3.2 Tat......................................................................................256
11.3 CPP Toxicity In Vivo....................................................................................256
Acknowledgments..................................................................................................258
Abbreviations.........................................................................................................258
References..............................................................................................................258
11.1 INTRODUCTION
The main application of CPPs is to use them for cargo delivery of bioactive polar
compounds lacking cellular uptake ability. These peptides may be used as carriers
245