RGD
sequence is a tripeptide composed of three amino acids: arginine
(R), glycine (G), and aspartic acid (D). The RGD peptide has a high
affinity to the integrin alpha v beta 3, which is overexpressed on
the membrane of many cancer cells and is attracted to areas of angiogenesis.
Proteinoids are biodegradable polymers based on amino acids which
are formed by bulk thermal step-growth polymerization mechanism. Hollow
proteinoid nanoparticles (NPs) may be formed
via
self-assembly
process of the proteinoid polymers. We propose using novel RGD-based
proteinoid polymers to manufacture NPs in which the RGD motif is self-incorporated
in the proteinoid backbone. Such P(RGD) NPs can act both as a drug
carrier (by encapsulation of a desired drug) and as a targeting delivery
system. This article presents the synthesis of four RGD proteinoids
with different RGD optical configurations, (
d
) or (
l
) arginine, glycine, and (
d
) or (
l
) aspartic acid,
in order to determine which configuration is optimal as a drug-targeting
carrier. These new RGD proteinoid polymers possess high molecular
weights and molecular weight monodispersity. Homonuclear nuclear magnetic
resonance methods were employed to predict the expected concentration
of RGD tripeptide sequence in the polymer. Near infrared fluorescent
NPs have been prepared by the encapsulation of indocyanine green (ICG)
dye within the different P(RGD) NPs. The dry diameters of the hollow
P(R
d
GD
d
), P(R
d
GD), P(RGD), and P(RGD
d
) NPs are 55 ±
13, 48 ± 9, 45 ± 11, and 42 ± 9 nm, respectively, whereas
those of the ICG-encapsulated NPs were significantly higher, 141 ±
24, 95 ± 13, 86 ± 11, and 87 ± 12 nm, respectively.
The ICG-encapsulated P(R
d
GD) NPs exhibited higher
selectivity toward epithelial injury, as demonstrated using an
in vitro
scratch assay, because the P(R
d
GD) NPs accumulated in the injured area at higher concentrations
when compared to other P(RGD) NPs with different chiralities. Therefore,
the P(R
d
GD) polymer configuration is the polymer
of choice for use as a targeted drug carrier to areas of angiogenesis,
such as in tumors, wounds, or cuts.