Biomedical Engineering Reference
In-Depth Information
for targeted gene delivery (Scheme 4.8). 68 PAMAM-pentaethylenehexamine
(PEHA) dendron polyplexes displayed the best gene transfer ability.
Conjugation of a PAMAM-PEHA dendron with a PEG spacer was conducted
via a click reaction, which was performed before amidation with PEHA. The
resultant PEG-PAMAM-PEHA copolymer was then coupled with an EGF
ligand. This compound showed 10-fold higher transfection efficiency in HuH-7
hepatocellular carcinoma cells compared to the ligand-free ones. Zhang et al.
reported that heparin and heparin-biotin were introduced into PAMAM/DNA
complexes via electrostatic interactions to form self-assembled PAMAM/
DNA/heparin and PAMAM/DNA/heparin-biotin terplexes, respectively. 69
The results indicated that these terplexes exhibited decreased cytotoxicity
after incorporation of heparin and heparin-biotin. Compared with PAMAM/
DNA and PAMAM/DNA/heparin complexes, the terplexes exhibited much
higher cellular uptake into HeLa cells due to the specific interactions between
biotin
d n 4 y 3 n g | 3
and
biotin
receptors
on
HeLa
cells,
which
led
to
the
enhanced
transfection activity.
The blood-brain barrier (BBB) exerts a neuroprotective function, as it
hinders the delivery of diagnostic and therapeutic agents to the brain. To
overcome this natural barrier, an intracerebral gene delivery strategy has been
extensively explored during the last two decades. A 29 amino acid peptide
derived from the rabies virus glycoprotein (RVG29) was exploited as a ligand
for efficient brain-targeting gene delivery due to its specific binding ability to
the nicotinic acetylcholine receptor (nAchR) on neuronal cells. Liu and co-
workers modified PAMAM with RVG29 through bifunctional PEG, and then
complexed it with DNA, yielding PAMAM-PEG-RVG29/DNA nanoparticles
(NPs). 70 PAMAM-PEG-RVG29/DNA NPs showed higher BBB crossing
efficiency than PAMAM/DNA NPs in an in vitro BBB model. In vivo imaging
showed that the NPs were preferably accumulated in the brain. Moreover, the
Scheme 4.8
Synthesis of ligand-modified PAMAM dendrimers via click chemistry.
 
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