Biomedical Engineering Reference
In-Depth Information
the blood-brain barrier into neural stem cells and endothelial progenitor cells in the brain
in regenerative medicine [228].
Krebs
et al
. used two types of calcium phosphate (CaP) NPs as a carrier for delivery of
BMP-2 pDNA [229]. In one type, pDNA was added to equal volumes of CaCl
2
and Na
2
HPO
4
in aqueous solution to quench the crystallization and coat the CaP crystals with BMP-2
DNA (Figure 9.4A). In the other type, CaP-DNA NPs were prepared by concurrent addition
of pDNA to the aqueous solution of CaCl
2
and Na
2
HPO
4
followed by the addition of
bovine serum albumin (BSA) to quench CaP crystallization [229] (Figure 9.4B). BMP-2
DNA was released more rapidly from DNA-BSA-CaP NPs compared with DNA-CaP NPs,
but both types exhibited sustained pDNA release. The encapsulation efficiency of DNA-
CaP and DNA-BSA-CAP NPs were 67% and 80%, respectively, and the DNA-CaP NPs
embedded in alginate gels formed bony tissue when injected subcutaneously in the back of
mice [229]. In a similar technique, Yang
et al
. showed that BMP-2-CaP pDNA NPs promote
the ondogenic differentiation of rat dental pulp stem cells [230].
Santos
et al
. used polyamidoamine (PAMAM) dendrimers as a carrier for BMP-2 gene
delivery toward osteogenic differentiation of MSCs [178, 231]. They reported that the BMP-2
pDNA with a β-galactosidase promotor region induced low-level transient expression of the
(A)
Ca
2+
PO
4
3-
CaP NP
DNA
(B)
Ca
2+
PO
4
3-
DNA
BSA
CaP -BSA NP
+
+
(C)
+
Cation-DNA
self-assembled NP
DNA
+
+
+
(D)
Magnetic
field
Magnetic
NP
Uptake trough
cell membrane
DNA
+
+
+
(E)
CPP enhanced
cell uptake
CPP
Magnetic
NP
DNA
Figure 9.4
Techniques for immobilization of genes (pDNA or siRNA) in/on nanoparticles (NPs).
(A) Encapsulation of pDNA in calcium phosphate (CaP) NPs by crystallization of calcium chloride
and disodium phosphate. (B) Encapsulation of pDA in CaP NPs with crystallization quenched with
bovine serum albumin (BSA). (C) Nanoparticle formation and pDNA encapsulation by complexation
of a cationic polymer with anionic DNA. (D) Complexation of a cationic polymer with anionic DNA
on iron oxide magnetic NPs for pDNA encapsulation and enhanced cell uptake by an external
magnetic field. (E) Complexation of a cationic polymer with anionic DNA on magnetic NPs followed
by conjugation of a cell-penetrating peptide (CPP) on the NP's surface for pDNA encapsulation,
enhanced NP internalization, and
in situ
stem-cell imaging.
