Biomedical Engineering Reference
In-Depth Information
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Scheme 4.11
Tumor-targeted arginine-rich amphiphilic lipopeptide gene vectors: (A)
chemical structure of arginine-rich peptides; (B) complex formed by
lipopeptide and DNA.
cardiomyocyte (PCM) (a 20-amino acid peptide) showed high selectivity for
cardiomyocytes, Nam et al. developed a cardiomyocyte-targeted Fas siRNA
delivery system using PCM-specific peptide-modified bioreducible poly(CBA-
DAH) (PCD).
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The impact of PCM conjugation on cellular uptake and
transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH
3T3 cells. Fas siRNA/PCM-polymer polyplexes exhibited significant Fas gene
silencing in rat cardiomyocytes under hypoxic conditions, leading to inhibition
of cardiomyocyte apoptosis.
Harris et al. developed electrostatically adsorbed poly(glutamic acid)-based
peptide coatings to alter the exterior composition of a core gene delivery
particle and thereby affect the tissue specificity of the gene delivery function in
vivo.
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They found that, with all coating formulations tested, the coatings
reduced the potential toxicity associated with uncoated cationic gene delivery
nanoparticles following systemic injection. Particles coated with a low
peptide:DNA weight ratio (w/w) form large 2 mm sized particles that could
facilitate specific gene delivery to the liver. The same particles coated at a
higher w/w form small 200 nm particles that can facilitate specific gene delivery
to the spleen and bone marrow. Thus, variations in nanoparticle peptide
coating density could alter the tissue specificity of gene delivery in vivo.
4.5.2 Cell-Penetrating Peptides
Cell-penetrating peptides (CPPs) are cationic polypeptides that can bind to
plasmid DNA via charge interaction and condensation, and which can shuttle
nucleic acids through cell membranes (Figure 4.8). CPP-based delivery systems
