Biomedical Engineering Reference
In-Depth Information
7.3 NM s FOR GENE DELIVERY
One of the most promising applications of NMs is gene delivery. NMs-mediated
gene delivery holds promise to cure many inheritable or acquired diseases that
are currently considered incurable. 52 NMs can be packed with DNA strands or
fragments very easily through the various conjugation or attachments methods
discussed in Chapter 3. In addition, because of the highly negative phosphate
backbone of DNA, it can easily be attached to positively charged NMs through
charge-charge interactions.
A number of NMs have been used as gene carriers 53 for both in vitro 54,55 and
in vivo gene delivery 56 that can theoretically reach a target site because of their
size and charge. 57 NMs can be used to conjugate 54,55 or to encapsulate 58 various
genetic materials in the form of DNA plasmids, RNA, and siRNA.
The group of Kneuer developed an approach to create positively charged
silica NPs through the simultaneous hydrolysis of tetraethoxysilane and N -( â -
aminoethyl)- ç -aminopropyltyiethoxysilane in a water-in-oil microemulsion
process. 55 The modification with amine active groups in silane resulted in silica
NPs that were 10-100 nm in diameter with zeta potential at +7 to +31 mV at
pH 7.4. The protonation of the amine surface resulted in positive charge on
the surface of the NMs that allowed for the linking of plasmid DNA (pDNA)
through electrostatic binding. 53 The DNA that was captured as DNA~NMs
complex can be released at alkaline pH (>10) or in the presence of high salt
concentrations (>2 mol/L NaCl) 59 . The same process was used by the group
of Bharali 60 to deliver a plasmid encoding enhanced green fluorescent protein
(EGFP) into mouse ventral midbrain and lateral ventricle. The presence of the
EGFP allowed fluorescent visualization of the successful transfection of neuron-
like cells. They also exhibited the application of the amino-modified silica NPs
for selective delivery of a nucleus-targeting fibroblast growth factor receptor
type 1 into mouse brain that led to significant inhibition of the incorporation of
bromodeoxyuridine into the subventricular zone and the adjacent rostral migra-
tory stream. 60
Studies encapsulating DNA or RNA inside biodegradable polymeric NPs for
controlled gene release have also been reported. 61-63 The encapsulation protects
the nucleic acids (NAs) from enzymatic digestion during transit in systemic cir-
culation, thereby allowing targeting to specific tissues or cells through the sur-
face functionalization of the NMs. 53 The encapsulation also provides protection
that avoids uptake of the NAs by the mononuclear phagocytic system because
of the presence of the NMs. 58 An approach using PEGylated gelatin NMs by the
acidic or basic hydrolysis of collagen 64 to encapsulate NAs have been used to
exhibit the delivery of a pDNA into NIH 3T3 murine fibroblast cells. 65
Targeted gene delivery has been made with ligands conjugated with antibodies on
biodegradable NMs encapsulating DNA. A DNA-polycation complex was formed
by mixing pDNA with Polyetheylene imine (PEI) at different ratios 66 . Monoclo-
nal antibody against the human epidermal growth factor receptor-2 (HER-2) using
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