Targeted Drug Delivery by Cathepsin Nanofiber Substrates
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Category |
Life Sciences and Biotechnology |
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Keywords |
Carriers, Cathepsin proteases, Tetra-peptides |
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Current development stage |
TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model |
Application
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The release of targeted drugs is often achieved by attaching the drug load to a carrier through specific peptide sequences which are cleaved by proteases that are highly expressed at the desired location.
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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.
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Improved release of anti-cancerous drug
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Substrates’ processes both in solution and within nanostructures.
Technology
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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.
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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.
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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.
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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
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A new platform for drug-delivery, targeted to pathologies with high cathepsins activity.
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A potential cancer immunotherapy solution
Patent Status
Published US-2019-0054035-A1
