Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Polymer Chemistry

Background:

• Glucose is a key targeting ligand for nanoparticles in biomedical applications.
• Single-chain polymer nanoparticles (SCNPs) are versatile 5-20 nm nanocarriers.
• Surface functionalization of SCNPs is crucial for targeted delivery, but current methods have limitations.

Purpose of the Study:

• To develop dual-reactive single-chain polymer nanoparticles (SCNPs) combining PFP-ester and click chemistry.
• To create glucose-functionalized SCNPs (glyco-SCNPs) with varying glucose densities and attachment positions.
• To evaluate the cellular uptake of these glyco-SCNPs in HeLa cancer cells.

Main Methods:

• Synthesized SCNPs with labile pentafluorophenyl (PFP) esters.
• Functionalized SCNPs with 1-amino-3-butyne via PFP-chemistry to create butyne-SCNPs.
• Conjugated 3-azido-propylglucose to butyne-SCNPs using copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry.
• Assessed cellular uptake in HeLa cancer cells.

Main Results:

• Successfully created dual-reactive SCNPs by integrating PFP-ester and CuAAC click chemistry.
• Generated glyco-SCNPs with tunable surface glucose density and distinct glucose attachment positions (C1 or C6).
• Observed increased cellular uptake of glyco-SCNPs with higher glucose surface density, independent of attachment position.

Conclusions:

• The developed dual-conjugation strategy offers enhanced versatility for SCNP surface functionalization.
• Glucose-decorated SCNPs demonstrate potential for targeted cancer cell delivery.
• This approach enables the creation of diverse libraries of multifunctional SCNPs for various biomedical applications.