Yissum - Research Development Company of the Hebrew University

Targeted Drug Delivery by Cathepsin Nanofiber Substrates

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

Cluster8
Cluster9

Cathepsin Nanofiber Substrates as Potential Agent for Targeted Drug Delivery
Project ID : 6-2017-4395

Yissum - Research Development Company of the Hebrew University

Description of the technology

Category

Life Sciences and Biotechnology

Keywords

Carriers, Cathepsin proteases, Tetra-peptides

Current development stage

TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model

Application

  • The release of targeted drugs is often achieved by attaching the drugload to a carrier through specific peptide sequences which are cleavedby proteases that are highly expressed at the desired location.
  • Cathepsins proteases, whose activity and expression are highly elevated in cancer and other pathologies, often serve as efficient enzymes for therapeutic release.

Our Innovation

A novel approach for developing self-assembled tetra-peptides serving as substrates of the cathepsin proteases.

  • Improved release of anti-cancerous drug
  • Substrates’ processes both in solution and within nanostructures.

Technology

  • A library of Phe-Phe-Lys-Phe (FFKF) tetra-peptide substrates (TPSs) was generated to serve as carriers for therapeutics to pathological tissues characterized by elevated protease activity.
  • It was demonstrated that in most cases elongation of the FF variant by two additional amino acids, including a charged lysine, did not impair the self-assembly of substrates into ordered nanofibers.
  • Degradation of TPS4 nanofibers by cathepsin B led to the release of 91.8 ± 0.3% of the incorporated anti-cancerous drug Doxorubicin from the nanofibers within 8 h while only 55±0.2% was released without enzyme treatment.
  • The intrinsic high cathepsin activity of tumor lysates can fully degrade TPS4 nanofibers.

Fig. 1: Drug release profile. Dox was precipitated by ammoniumsulfate to generate Dox particles (DPs), TPS4 was added and allowed to assemble overnight. Bright field (a) and fluorescentmicroscopy of DP-TPS4 (b). Analysis of DPs alone forming unstructured aggregates as well as fibers (white arrow), SEM(c) and TEM(d). Analysis ofDPs-TPS4 showing defined nanofibers by SEM(e) and TEM(f). Release profile of Dox fromDP-TPS4 nanostructure in the presence and absence of cathepsin B (g). After 8 h 91.8±0.3% of total drug was released from DP-TPS4 following cathepsin B treatment. Results are described with standard error, ** p b 0.01, *** p b 0.001, **** p b 0.0001.

Opportunity

  • A new platform for drug-delivery, targeted to pathologies with high cathepsins activity.
  • A potential cancer immunotherapy solution

Project manager

Mel Larrosa
VP Business Development Healthcare

Project researchers

Galia Blum
HUJI, School of Medicine - IMRIC
School of Pharmacy- Institute for Drug Research

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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