2. Academic Validation
  3. A Customizable Antibody Delivery Strategy Using Fc-Affinity Ligands

A Customizable Antibody Delivery Strategy Using Fc-Affinity Ligands

  • ACS Biomater Sci Eng. 2026 Apr 13;12(4):2228-2242. doi: 10.1021/acsbiomaterials.5c02112.
Daniela Isaacs-Bernal 1 2,  Noor E Bahsoun 1 2,  Lia Huo 2 3,  Gennady Poda 4 5,  Dima Kozakov 6,  Molly S Shoichet 1 2 3 5
Affiliations

Affiliations

  • 1 Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.
  • 2 Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • 3 Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
  • 4 Drug Discovery Program, Ontario Institute for Cancer Research, 661 University Avenue, Toronto, Ontario M5G 0A3, Canada.
  • 5 Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.
  • 6 Laufer Center for Physical and Quantitative Biology, Stony Brook University, 100 Nicolls Road, Stony Brook, New York 11794-3600, United States.
PMID: 41789782 DOI: 10.1021/acsbiomaterials.5c02112
Abstract

Affinity-controlled release provides a versatile approach for the delivery of proteins from hydrogel systems by harnessing noncovalent interactions between a molecule of interest and a binding ligand. We present a strategy for the controlled release of native antibodies by leveraging affinity interactions with peptide ligands specific to the fragment crystallizable (Fc) region. Two Fc-binding ligands (FcLs) were engineered using distinct spacers, yielding different degrees of equilibrium dissociation constants (KD) for the Fc region of human IgG1: 2.54 ± 0.03 × 10-8 M (HWRGWV-GAKSKG; FcL1) and 3.01 ± 0.09 × 10-7 M (HWRGWV-K(PEG); FcLPEG). These ligands were immobilized within a chemically cross-linked hyaluronan-oxime hydrogel, where controlled release of bioactive bevacizumab was observed with FcL1 but not with the lower-affinity FcLPEG. To further explore the versatility of this approach, FcL1 was incorporated into a physically cross-linked hyaluronan-methylcellulose hydrogel, demonstrating tunable release of multiple IgG1 antibodies, including bevacizumab and adalimumab, each over a 7-day period. Together, this work demonstrates a broadly applicable strategy to tune antibody release.

Keywords

affinity ligand; antibody; bevacizumab; controlled release; hydrogels; protein delivery.

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