Biomedical Engineering Reference
In-Depth Information
cytometry and confocal laser scanning microscopy (CLSM) analysis generally
show that FA-conjugated nanoparticles exhibit higher cellular uptake than the
ones without FA conjugation. Meanwhile, other recognition agents have been
developed to improve the targeting efficiency, such as Arg-Gly-Asp oligopep-
tides (RGD) and boronic acid. RGD with biological activity has been widely
applied in drug delivery systems, which selectively targets at the receptors of
a
v
b
3
integrin overexpressed in rapidly growing tumor capillaries during
angiogenesis. Antibodies are also widely used in targeting the specific tumor
tissues, such as the anti-EGFR antibody and the anti-RON antibody.
45-55
By
comparison with common antibody-antigen recognition, multivalent sugar-
protein binding has received much attention for the fabrication of targeted
delivery systems, and has a lower cost and immunogenicity. It should also be
mentioned that the effective combination of boronic acid with saccharide can
be applied when recognizing saccharide on the surface of glycoproteins in the
tumor tissue. The utility of peptide and boronic acids may accelerate the access
to vast diagnostic methods economically.
56,57
Another obvious phenomenon
occurring in tumor tissues is that multivalent saccharide binding by lectins is
important for the process of cancer metastasis. The sequence transformation of
carbohydrate arrays of glycoprotein on the cancer cells has altered the
tethering ability of lectin and saccharide during carcinogenesis, which is a hint
for targeting. The mutual interaction of lection and glycoprotein is similar to
that of antibody and antigen. Interest in lectin specifically recognizing
saccharide moieties involved in the glycoprotein is increasing due to their
potential as therapeutics/diagnostics for a variety of diseases such as cancers.
58
The efficient modification of these functional targeting groups on the delivery
systems is the key point for realizing the functional transportation to the tumor
tissues. Therefore, HBPs with numerous terminal groups and cavities have
burgeoned rapidly over the past decades.
Prabaharan et al. prepared a folate-conjugated amphiphilic hyperbranched
block copolymer [H40-star-(PLA-b-PEG/PEG-FA)] as a carrier for tumor-
targeted drug delivery.
59
The synthetic drug delivery system comprised a
dendritic Boltorn H40 core, a hydrophobic poly(
L
-lactide) (PLA) inner shell,
and a hydrophilic methoxy-poly(ethylene glycol) (PEG) and folate-conjugated
poly(ethylene glycol) (PEG-FA) outer shell. The hydrophobic anticancer drug
DOX was encapsulated into the core of the micelles. The release pattern of the
DOX-loaded micelles manifested an initial burst release within 4 h and an
ensuing sustained release of the entrapped DOX over a period of about 40 h.
Cellular uptake of the DOX-loaded HBP micelles was found to be higher than
that of the DOX-loaded H40-star-(PLA-b-PEG) micelles because of the folate-
receptor-mediated endocytosis, thereby providing higher cytotoxicity against
the 4T1 mouse mammary carcinoma cell line. The result indicates that the
H40-star-(PLA-b-PEG/PEG-FA) micelles prepared from HBP are promising
as tumor-targeted drug delivery nanocarriers. With many terminal groups on
H40, the effect of targeting is better than that of linear polymers. The folate
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