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328 Cell-Penetrating Peptides: Processes and Applications
Cargo CPP
FIGURE 15.1 CPP delivery. CPP is able to deliver various types of biological active molecules
through plasma membrane; some of them can even deliver cargo molecules into nucleus.
membrane lipid bilayer, 4 and use of peptide/protein-mediated translocation signals. 5,6
Recently reported cell-penetrating peptides (CPP), including the HIV–Tat, 7,8 the third
helix of the homeodomain of Antennapedia, 9 transportant, 10,11 a peptide derived from
antiDNA monoclonal antibody, 1,2 VP22 herpes virus protein, 13,14 and other synthetic
peptides, 15,16 provide a new way of delivering cargo molecules through cellular
barrier (Figure 15.1). The large number of CPPs have been used as efficient delivery
vehicles for various biological active molecules, such as proteins, 7,17-23 peptides, 8,24,25
oligonucleotides, 26-28 peptide nucleic acid, 29 plasmid DNA, 30-32 and imaging compounds
(Table 15.1). 33-36
Magnetic materials such as superparamagnetic nanoparticles, ferromagnetic
beads, and paramagnetic chelators already play important roles in biotechnology
and clinical medicine. However, their applications could be even broader if they
could be efficiently delivered into cells rather than attaching them to the cell surface.
Internalization would allow an entirely new application spectrum of these materials,
including (1) in vivo tracking of labeled immune cells in intact micro- and macroenvironments
over time, (2) tracking of stem and progenitor cells by imaging,
(3) magnetic isolation of in vivo homed cells, and (4) using magnetic materials as
nanosensors for intracellular readouts of protein or DNA and imaging gene expression.
In this chapter we first describe conjugation strategies for attaching CPPs to
different materials, then summarize our studies on labeling cells with Tat-assisted
magnetic probes.
15.2 CONJUGATION TACTICS
Cell
Nucleus
We and other groups have used a number of different strategies to bioconjugate
CPPs to payloads; the following section reviews some of them. Most frequently