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Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry
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Boronate-mediated biologic delivery.

Gregory A Ellis1, Michael J Palte, Ronald T Raines

  • 1Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Journal of the American Chemical Society
|February 7, 2012
PubMed
Summary
This summary is machine-generated.

Boronic acids can improve the delivery of large drugs into cells by interacting with cell surface sugars. This novel approach offers a non-damaging method for enhanced macromolecular drug delivery into mammalian cells.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Drug Delivery

Background:

  • Macromolecular drug delivery into cells is hindered by inefficient cellular uptake mechanisms.
  • Cell surfaces are rich in saccharides, which present potential targets for drug carriers.
  • Boronic acids are known to form reversible covalent bonds with diols found in saccharides.

Purpose of the Study:

  • To investigate the potential of boronic acids as carriers for enhancing cytosolic delivery of macromolecular drugs.
  • To demonstrate a non-cationic strategy for improving the cellular entry of polar macromolecules.

Main Methods:

  • Conjugating pendant boronic acids to a protein toxin.
  • Assessing the cellular uptake and cytosolic delivery efficiency of the modified protein toxin in mammalian cells.
  • Utilizing the interaction between boronic acids and cell-surface saccharides for targeted delivery.

Main Results:

  • Pendant boronic acids significantly enhanced the cytosolic delivery of the protein toxin.
  • The boronate ester formation with cell-surface saccharides facilitated cellular entry.
  • This method proved effective for delivering a polar macromolecule into mammalian cells.

Conclusions:

  • Boronic acids serve as effective noncationic carriers for macromolecular drug delivery.
  • The interaction with cell-surface saccharides is a viable strategy for improving drug internalization.
  • This approach broadens the possibilities for delivering large, polar therapeutic molecules into cells.