Biomedical Engineering Reference
In-Depth Information
Nucleus
Lysosome
Small molecules
Proteins
DNA
siRNA
Endosome
A typical loaded nanoparticle
Figure 13.3
Scheme of nonviral delivery nanocarriers. Internalized nanoparticles escape the
endosome and release their cargo.
Delivery of bioactive agents into stem cells can be a potent strategy to direct their
differentiation into specific cell types, as seen in Figure 13.3. When the nanoparticles are
formed the next key step in delivery is endocytosis. For efficient uptake it is important for
nanocarriers to have an overall positive charge so that they will be electrostatically attracted to
the negatively charged proteoglycan cell surface. The transfection efficiency of carriers is
dependent on surface charge. When the surface charge becomes less positive, adsorptive endo-
cytosis decreases, which results in reduced transfection efficiency. The size of the nanocarriers
affects uptake and smaller particles (about 100 nm) have the most efficient uptake. Throughout
uptake and internalization, nanocarriers are encased into endosomes and become part of the
endosomal sorting pathway. As the next step, the bioactive agent must be released from the
nanocarrier. Polycationic carriers have enhanced intracellular delivery due to their ability to
directly enable endosomal escape through the “proton sponge” mechanism [4, 5].
Nanocarriers are formed by numerous biomaterials for intracellular delivery into stem
cells [7]. These biomaterials consist of organic, inorganic, and organic-inorganic hybrid
nanocomposites.
Organic materials are classified into two categories: natural and synthetic polymers. The
natural organic materials include chitosan (CS), hyaluronic acid (HA), and dextran, among
others. Synthetic organic polymers allow a high level of design flexibility for preparation of
nanocarriers. These polymers are divided into three groups. Bioreducible polycationic
polymers show reduced cytotoxicity and controlled intracellular release of genes, leading
to increased transfection efficiency. Examples of these polymers include branched/linear
polyethylenimine (PEI) and branched poly(disulfide amine) (B-PDA) among others.
Biodegradable polymers have the advantage of being eliminated after the bioactive agents
are released, in the form of nontoxic degradation products such as the polyesters poly(lactide-
co-glycolide) (PLGA), poly (β-amino ester) (PBAE), polybutylcyanoacrylate (PBCA), and
poly(ethylene glycol) (PEG). The final group comprises dendrimers or poly (amido amine)s
(PAMAM). Polymeric nanocarriers are of interest due to their low cost, facilitated produc-
tion, and controllable toxicity, based on parameters such as ionic charge, chemistry, and
chain length.
Inorganic carriers consist of silica (SiNP), calcium phosphate (CPNP) and magnetic
(MNP) nanoparticles. The organic-inorganic hybrid carriers are combinations of polymers
