Smart Glycopolymeric Nanoparticles for Multivalent Lectin Binding and Stimuli-Controlled Guest Release

Area of Science:

• Supramolecular Chemistry
• Polymer Science
• Nanotechnology

Background:

• Self-assembly is a key process in creating nanostructures.
• Stimuli-responsive materials offer controlled release capabilities.
• Lactose moieties can mediate specific biological interactions.

Purpose of the Study:

• To synthesize and characterize novel polymer nanoparticles (NPs) with a self-complementary supramolecular binding motif.
• To investigate the stimuli-responsive self-assembly and disassembly of these NPs.
• To evaluate the potential of these NPs for targeted delivery and cargo encapsulation.

Main Methods:

• Synthesis of a polymer with guanidiniocarbonyl pyrrole carboxylate zwitterion (GCP-zwitterion) and lactose moieties.
• Characterization of nanoparticle formation and size using dynamic light scattering.
• Stimuli-responsive studies involving pH changes (acid/base).
• Lectin binding assays (peanut agglutinin) and agglutination experiments.
• Encapsulation and release studies with Nile red.
• Cellular uptake studies with HEK 296T, HeLa, and Hep2G cell lines.

Main Results:

• Polymer self-assembly into nanoparticles (<40 nm) at neutral pH via GCP-zwitterion cross-linking.
• Stimuli-responsive disassembly of NPs upon addition of acid or base due to GCP protonation/deprotonation.
• Confirmation of multivalent lectin binding through agglutination.
• Successful uptake and release of hydrophobic Nile red cargo.
• Selective cellular uptake observed in Hep2G cells expressing the lactose-specific asialoglycoprotein receptor, with no interaction in other cell lines.

Conclusions:

• The synthesized polymer effectively self-assembles into stimuli-responsive nanoparticles.
• The NPs exhibit controlled cargo loading and release capabilities.
• The lactose moieties enable selective targeting and cellular uptake in specific cell types, demonstrating potential for targeted drug delivery.