Biorecognition: A key to drug-free macromolecular therapeutics

Jiyuan Yang, Lian Li, Jindrich Kopecek

Research output: Contribution to journalReview article

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Abstract

This review highlights a new paradigm in macromolecular nanomedicine – drug-free macromolecular therapeutics (DFMT). The effectiveness of the new system is based on biorecognition events without the participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. B-cell CD20 receptors and Non-Hodgkin lymphoma (NHL) were chosen as the first target. Exposing cells to a conjugate of one motif with a targeting ligand decorates the cells with this motif. Further exposure of decorated cells to a macromolecule (synthetic polymer or human serum albumin) containing multiple copies of the complementary motif as grafts results in receptor crosslinking and apoptosis induction in vitro and in vivo. The review focuses on recent developments and explores the mechanism of action of DFMT. The altered molecular signaling pathways demonstrated the great potential of DFMT to overcome rituximab resistance resulting from either down-regulation of CD20 or endocytosis and trogocytosis of rituximab/CD20 complexes. The suitability of this approach for the treatment of blood borne cancers is confirmed. In addition, the widespread applicability of DFMT as a new concept in macromolecular therapeutics for numerous diseases is exposed.

LanguageEnglish (US)
Pages11-23
Number of pages13
JournalBiomaterials
Volume190-191
DOIs
StatePublished - Jan 1 2019

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Cell death
Crosslinking
Medical nanotechnology
Oligonucleotides
Macromolecules
Grafts
Pharmaceutical Preparations
Peptides
Blood
Molecular weight
Ligands
Cells
Apoptosis
Nanomedicine
Polymers
Therapeutics
Endocytosis
Serum Albumin
Non-Hodgkin's Lymphoma
B-Lymphocytes

Keywords

  • Biorecognition
  • Coiled-coil peptides
  • Drug-free macromolecular therapeutics
  • Human serum albumin
  • Morpholino oligonucleotides
  • N-(2-hydroxypropyl)methacrylamide copolymer

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Biorecognition : A key to drug-free macromolecular therapeutics. / Yang, Jiyuan; Li, Lian; Kopecek, Jindrich.

In: Biomaterials, Vol. 190-191, 01.01.2019, p. 11-23.

Research output: Contribution to journalReview article

Yang, Jiyuan ; Li, Lian ; Kopecek, Jindrich. / Biorecognition : A key to drug-free macromolecular therapeutics. In: Biomaterials. 2019 ; Vol. 190-191. pp. 11-23.
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