Biomedical Engineering Reference
In-Depth Information
Poly(β-amino esters)
One interesting type of cationic and hydrolytically degradable polymeric nanocarrier for
intracellular delivery is PBAE, which was first developed by Lynn and Langer in 2000 [25].
Poly(β-amino ester)s are synthesized by the conjugate addition of amine monomers to diac-
rylates. The condensation of the gene inside PBAE nanocarriers can greatly increase the
retention time and provide better protection against nuclease degradation. Poly(β-amino
ester)s have the potential for structural diversity as well as the ability for ligand-specific
uptake. They can efficiently condense DNA to form nanocarriers. These nanocarriers have
the capability to buffer the endosome and facilitate endosomal escape, as well as having a high
efficacy both
in vitro
and
in vivo
. In comparison with PEI, they possess reduced cytotoxicity
and biodegradability, and the ability for triggered genes release within the stem cell [26, 27].
Yang
et al
. [28] developed PBAE nanoparticles that could deliver the vascular endothelial
growth factor (VEGF) gene to hMSCs and hECS-derived cells to promote angiogenesis.
Interestingly, their effort led to enhancement of human VEGF production, cell viability, and
engraftment into tissue target-producing vessels. This delivery system showed that stem cells
nanoengineered with PBAE could be therapeutic tools for vascularizing tissue constructs
and treating ischemic disease.
Green
et al
. [29] assembled PBAE with DNA to prepare submicron and positively charged
polymeric nanoparticles for efficient gene delivery in hESCs. These nanocarriers exhibited
low toxicity and did not unfavorably influence colony morphology or cause nonspecific
differentiation of the hESCs. In an additional work [30], the same group have studied the
capacity of cystamine-terminated PBAE for delivery of siRNA to hMSCs for osteogenic
differentiation. In this delivery system the cystamine-terminated polymer is bound to siRNA
prior to exposure to a reducing environment, which efficiently releases siRNA. Thus PBAE
terminated by cystamine can form tight initial interactions with its cargo and then cause an
efficient, environmentally triggered delivery in the cytoplasm. These researchers in another
work [31] have used PBAE nanocarriers for intracellular delivery of genes to primary glio-
blastoma (GB) cells as well as GB tumor stem cells
in vitro
, with low nonspecific toxicity and
transfection efficiencies. They developed DNA nanocarriers that remained relatively
unchanged in normal serum and could also be stored for at least 3 months in a ready-to-use
state with no detectable drop in efficacy, which showed their potential in practical or clinical
settings. In this case the specificity and transfection for GB cells was higher than in healthy
astrocytes and stem cells.
Poly(lactide-co-glycolide)
Poly(lactide-co-glycolide) is a biodegradable, biocompatible, and US Food and Drugs
Administration approved biomaterial that has aroused considerable interest among
researchers who seek to develop biodegradable nanocarriers [32]. The PLGA nanoparticles
have widely been used for delivery of biologically active agents and have the capacity for
cell internalization [33]. Poly(lactide-co-glycolide) have the intrinsic capacity to escape
endosomal degradation. The mechanism of this escape involves direct interaction of PLGA
with the endosomal membrane owing to selective reversal of the surface charge of PLGA
(from anionic to cationic) under acidic conditions [34].
The complexation of DNA with PLGA nanoparticles has allowed robust gene expression
in stem cells. Poly(lactide-co-glycolide) can be modified with other polymers such as PEI.
Polyplexing with PEI has been shown to enhance cellular uptake of DNA complexed to
PLGA nanoparticles both
in vitro
and
in vivo
. Research has shown that the incorporation of
PLGA nanoparticles that contain growth factor in embryoid bodies caused enhanced
vascular differentiation of hESCs [35]. Incorporation of these nanoparticles minimally
