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Area of Science:

  • Bioconjugation Chemistry
  • Metabolic Glycoengineering
  • Nanomaterials in Biology

Background:

  • Cell-type selective metabolic labeling of glycans is challenging in complex biological settings.
  • Targeted delivery of unnatural sugars is crucial for specific glycan modification.
  • Metal-organic frameworks (MOFs) offer potential for controlled drug/molecule delivery.

Purpose of the Study:

  • To develop a novel tool for cell-type selective metabolic glycan labeling.
  • To achieve targeted delivery of unnatural sugars using receptor-mediated endocytosis.
  • To enable specific glycoengineering of target cells in mixed populations.

Main Methods:

  • Encapsulation of azido sugar (ManNAz) into mannosyl ligand-modified MOF (MIL-101-Man).
  • Utilizing mannose receptor (MR) targeting for specific cell uptake.
  • Employing fluorescence-based biorthogonal cell labeling for detection.
  • Co-culture assays to demonstrate cell-type specificity.

Main Results:

  • MIL-101-Man demonstrated receptor-dependent uptake via MRs.
  • Released ManNAz was metabolically incorporated into cellular glycans.
  • Targeted glycoengineering of MR-overexpressing cells was achieved in co-culture settings.
  • High specificity was observed over cells with minimal MR expression.

Conclusions:

  • The developed MOF-based tool enables targeted delivery of unnatural sugars for metabolic glycoengineering.
  • This approach facilitates cell-type selective glycan modification in complex biological environments.
  • The study provides an effective strategy for receptor-targeted glycoengineering of specific cell populations.