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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous polysaccharides with affinity for CD44 receptors.
• CD44 receptors are overexpressed in various tumor types, making them a target for cancer therapy.

Purpose of the Study:

• To synthesize HA- and CD-modified poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) nanoparticles.
• To encapsulate DOTAT/pDNA (D/P) lipoplex within these nanoparticles for CD44 receptor-targeted gene delivery.

Main Methods:

• Synthesis of HA- and CD-modified PLGA-PEG copolymers.
• Encapsulation of D/P lipoplex into nanoparticles.
• Characterization of nanoparticle size, zeta potential, and drug release kinetics.
• Evaluation of cytotoxicity and transfection efficiency in CD44-positive and negative cell lines.

Main Results:

• CD-modified nanoparticles (NPs) exhibited smaller particle size (186.8 nm) compared to HA-modified NPs (270.2 nm).
• Both NP types demonstrated pH-dependent drug release, with faster release at pH 4.0.
• CD-modified NPs showed lower cytotoxicity and significantly higher transfection efficiency in CD44-positive U87 cells compared to CD44-negative HepG2 cells.

Conclusions:

• CD-modified PLGA-PEG nanoparticles demonstrate high selectivity for CD44-positive cancer cells.
• These nanoparticles exhibit low cytotoxicity in normal cells, indicating their potential as effective gene delivery carriers.