American Society of Hirudotherapy

A substrate-selective enzyme-catalysis assembly strategy for oligopeptide hydrogel-assisted combinatorial protein delivery

Nanomedicine study published in Nano Letters (2017)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDrug DevelopmentSalivary PharmacologyJiang T et al. · Nano letters, 2017

Abstract

Oligopeptide hydrogels for localized protein delivery have considerable potential to reduce systemic side effects but maximize therapeutic efficacy. Although enzyme catalysis to induce formation of oligopeptide hydrogels has the merits of unique regio- and enantioselectivity and mild reaction conditions, it may cause the impairment of function and activity of the encapsulated proteins by proteolytic degradation during gelation. Here we report a novel enzyme-catalysis strategy for self-assembly of oligopeptide hydrogels using an engineered protease nanocapsule with tunable substrate selectivity. The protease-encapsulated nanocapsule shielded the degradation activity of protease on the laden proteins due to the steric hindrance by the polymeric shell weaved around the protease, whereas the small-molecular precursors were easier to penetrate across the polymeric network and access the catalytic pocket of the protease to convert to the gelators for self-assembling hydrogel. The resulting oligopeptide hydrogels supported a favorable loading capacity without inactivation of both an antiangiogenic protein, hirudin and an apoptosis-inducing cytokine, TRAIL as model proteins. The hirudin and TRAIL coloaded oligopeptide hydrogel for combination cancer treatment showed enhanced synergistic antitumor effects both in vitro and in vivo.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsAngiogenesis InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCapsulesCatalysisCell Line, TumorCell SurvivalCytokinesDrug CarriersDrug LiberationHirudinsHumans

Summary

Substrate-selective enzyme catalysis to assemble oligopeptide hydrogels for combinatorial protein delivery — applied to bring together hirudin and other therapeutic proteins.

Why This Matters for Hirudotherapy

This study developed a substrate-selective enzyme-catalysis assembly strategy for oligopeptide hydrogels using engineered protease nanocapsules with tunable substrate selectivity, demonstrating favorable loading capacity without inactivation of both hirudin (as an antiangiogenic model protein) and TRAIL (an apoptosis-inducing cytokine). The protease nanocapsule's polymeric shell shielded encapsulated proteins from degradation while allowing small-molecular precursors to access the catalytic pocket for hydrogel formation, and the co-loaded hirudin/TRAIL hydrogel showed enhanced synergistic antitumor effects both in vitro and in vivo. This is relevant to ASH as it demonstrates a novel delivery platform that preserves hirudin's biological activity during encapsulation and localized release. The caveat is that this is a preclinical biomaterials and drug delivery study in which hirudin is used primarily as a model antiangiogenic protein for oncology applications rather than for anticoagulation or hirudotherapy; the relevance to leech-based therapy is limited to drug delivery methodology.

Citation

A substrate-selective enzyme-catalysis assembly strategy for oligopeptide hydrogel-assisted combinatorial protein delivery.

Jiang T et al. · Nano letters, 2017

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.