Biomedical Engineering Reference
In-Depth Information
peptide nanofiber microenvironments recruited progenitor cells that express
endothelial markers, as determined by staining with isolectin and for the
endothelial-specific protein platelet-endothelial cell adhesion molecule. Vas-
cular smooth muscle cells were recruited to the microenvironment and ap-
pear to form functional vascular structures. After the endothelial cell pop-
ulation, cells that expressed sarcomeric actin and the transcription factor
Nkx2.5 infiltrated the peptide microenvironment. When exogenous donor
green fluorescent protein-positive neonatal cardiomyocytes were injected
with the self-assembling peptides, transplanted cardiomyocytes in the pep-
tide microenvironment survived and also augmented endogenous cell re-
cruitment [107].
4.3
Gene and Drug Delivery
The lack of predictable safety and efficacy standards in somatic gene ther-
apy systems, have brought the whole field to a crossroads. Replication-
incompetent viruses, naked DNA injection and liposomal agents have been
the predominant means of genetic transfer. To date, there has been little last-
ing impact in the typical practice of medicine conferred by these gene therapy
technologies. The crux of today's gene therapy dilemma is still the same as it
has always been: efficient, safe, targeted delivery and persistent gene expres-
sion [108, 109].
Peptide-based gene delivery agents are emerging as alternatives for safer
in vivo delivery. The main attraction of these peptide systems is their versa-
tility. Peptide-based delivery systems have the ability to deliver therapeutic
proteins, bioactive peptides, small molecules and any size of nucleic acids.
The use of these agents allows the researcher to intervene at multiple levels
in the cells genetics and biochemistry and is a fundamental new technology
in the gene therapy field [110, 111]. Peptide-delivery agents are more like tra-
ditional pharmacological drugs than gene therapy vectors. With the past to
guide us, a critical re-evaluation of the best characteristics for an ideal deliv-
ery system is in order. The desirable features may include the items displayed
in the paper [112].
We developed a series of surfactant peptides comprising a hydrophobic tail
attached to a polar headgroup consisting of one to two positively charged
residues at the
C
-or
N
-terminus, one example being LLLLLLKK. These pep-
tides self-assemble in water to produce nanovesicles and nanotubes [54] as re-
ported in a Science News commentary [113] and in recent reviews [114, 115];
these peptides have been used as DNA delivery vehicles. When placed in a so-
lution of DNA, the positively charged peptides self-assembled into a nanotube
or vessel, encapsulating the negatively charged DNA. This “minivan” was then
able, at least in some cases, to deliver the DNA to growing cells as the mini-
van surface can be tagged with a marker that is specific to a particular cell
