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Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery

Authors Lin WJ, Lee WC

Received 19 January 2018

Accepted for publication 24 April 2018

Published 10 July 2018 Volume 2018:13 Pages 3989—4002

DOI https://doi.org/10.2147/IJN.S163149

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Farooq Shiekh

Peer reviewer comments 5

Editor who approved publication: Dr Linlin Sun


Wen Jen Lin,1,2 Wei Chi Lee1

1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan

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.

Keywords: hyaluronic acid, chondroitin sulfate, poly(lactide-co-glycolide)

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