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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Nanomedicine
2018 ; 13
(ä): 3989-4002
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Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting
ability for gene delivery
#MMPMID30022822
Lin WJ
; Lee WC
Int J Nanomedicine
2018[]; 13
(ä): 3989-4002
PMID30022822
show ga
BACKGROUND: Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous
polysaccharides. In recent years, they have aroused the interest of scientists
because of specific binding to CD44 receptors, which are overexpressed in several
types of tumors. METHODS: In this study, HA- and CD-modified
poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymers were
synthesized and applied to encapsulate 1,2-Dioleoyl-3-trimethylammonium-propane
(DOTAP)/pDNA (D/P) lipoplex as CD44 receptor targeting gene delivery
nanoparticles (NPs). RESULTS: The particle size of CD-PEG-PLGA-D/P (186.8 ± 21.7
nm) was smaller than that of HA-PEG-PLGA-D/P (270.2 ± 13.8 nm), with narrow size
distribution, and both HA-PEG-PLGA-D/P NPs and CD-PEG-PLGA NPs possessed negative
zeta potentials (-39.63 ± 5.44 mV and -38.9 ± 2.0 mV, respectively), which
prevent erythrocytes from agglutination. Both NPs exhibited pH-dependent release
and had faster release in pH 4.0 than in pH 7.4. Generally, the CD-PEG-PLGA-D/P
NPs possessed less cytotoxicity than HA-PEG-PLGA-D/P NPs. The D/P-loaded
HA-PEG-PLGA and CD-PEG-PLGA NPs expressed significantly higher transfection in
CD44 high-expressed U87 (30.1% ± 2.1% and 40.7% ± 4.3%, respectively) than in
CD44-negative HepG2 (3.3% ± 1.5% and 1.4% ± 1.0%, respectively) (p < 0.001). It
was revealed that the endocytosis of HA-PEG-PLGA-D/P NPs was majorly dominated by
macropinocytosis and the endocytosis of CD-PEG-PLGA-D/P NPs was dominated by
clathrin-mediated endocytosis pathway (p < 0.001). CONCLUSION: The high
selectivity to CD44-positive U87 cancer cells and low cytotoxicity in L929 normal
cells assured the promising potential of CD-PEG-PLGA NPs as gene delivery
nano-carriers.