Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
Journal
International Journal of Nanomedicine
Journal Volume
13
Pages
3989-4002
Date Issued
2018
Author(s)
Lee W.C.
Abstract
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. ? 2018 Lin and Lee.
Subjects
Chondroitin sulfate; Hyaluronic acid; Poly(lactide-co-glycolide)
SDGs
Other Subjects
1,2 dioleoyl 3 trimethylammoniopropane; antineoplastic agent; chondroitin sulfate; clathrin; copolymer; Hermes antigen; hyaluronic acid; lipoplex; macrogol; nanocarrier; nanoparticle; plasmid DNA; polyglactin; 1,2-dioleoyloxy-3-(trimethylammonium)propane; CD44 protein, human; chondroitin sulfate; DNA; hyaluronic acid; hyaluronic acid binding protein; macrogol; monounsaturated fatty acid; nanoparticle; polyester; polyethylene glycol-poly(lactide-co-glycolide); polysaccharide; quaternary ammonium derivative; Article; blood clotting; controlled study; cytotoxicity; drug targeting; endocytosis; gene delivery system; glioblastoma cell line; Hep-G2 cell line; human; human cell; macropinocytosis; nanoencapsulation; particle size; pH; synthesis; zeta potential; animal; cell survival; chemistry; drug release; erythrocyte; gene transfer; metabolism; mouse; plasmid; proton nuclear magnetic resonance; static electricity; Animals; Cell Survival; Chondroitin Sulfates; DNA; Drug Liberation; Endocytosis; Erythrocytes; Fatty Acids, Monounsaturated; Gene Transfer Techniques; Hep G2 Cells; Humans; Hyaluronan Receptors; Hyaluronic Acid; Mice; Nanoparticles; Particle Size; Plasmids; Polyesters; Polyethylene Glycols; Polysaccharides; Proton Magnetic Resonance Spectroscopy; Quaternary Ammonium Compounds; Static Electricity
Type
journal article