2. Academic Validation
  3. Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics

Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics

  • Nat Nanotechnol. 2025 Oct;20(10):1502-1513. doi: 10.1038/s41565-025-01981-6.
Brett H Pogostin 1,  Samuel X Wu 1,  Michael J Swierczynski 2,  Christopher Pennington 3,  Si-Yang Li 4,  Dilrasbonu Vohidova 1,  Erin H Seeley 5,  Anushka Agrawal 1,  Chaoyang Tang 1,  Marina H Yu 1,  Arghadip Dey 2,  Sofia Hernandez 6,  Jacob Cabler 1,  Omid Veiseh 1,  Eric L Nuermberger 4,  Zachary T Ball 2,  Jeffrey D Hartgerink 7 8,  Kevin J McHugh 9 10
Affiliations

Affiliations

  • 1 Department of Bioengineering, Rice University, Houston, TX, USA.
  • 2 Department of Chemistry, Rice University, Houston, TX, USA.
  • 3 Shared Equipment Authority, Rice University, Houston, TX, USA.
  • 4 Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 5 Department of Chemistry, University of Texas at Austin, Austin, TX, USA.
  • 6 Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.
  • 7 Department of Bioengineering, Rice University, Houston, TX, USA. [email protected].
  • 8 Department of Chemistry, Rice University, Houston, TX, USA. [email protected].
  • 9 Department of Bioengineering, Rice University, Houston, TX, USA. [email protected].
  • 10 Department of Chemistry, Rice University, Houston, TX, USA. [email protected].
PMID: 40931056 DOI: 10.1038/s41565-025-01981-6
Abstract

Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion. Here, to overcome this challenge, we present self-assembling boronate ester release (SABER) multidomain peptides capable of engaging in dynamic covalent bonding with payloads containing boronic acids. As examples, we demonstrate that SABER hydrogels can prolong the release of boronic acid-containing small-molecule drugs and boronic acid-modified biologics such as Insulin and antibodies. Pharmacokinetic studies reveal that SABER hydrogels extend the therapeutic effect of ganfeborole from days to weeks, preventing Mycobacterium tuberculosis growth compared with oral administration in an Infection model. Similarly, SABER hydrogels extended Insulin activity, maintaining normoglycemia for 6 days in diabetic mice after a single injection. These results suggest that SABER hydrogels present broad potential for clinical translation.

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