A new platform of drug-delivery for Cancer Immunotherapy and for other Pathologies with high Cathepsins activity
Background
-
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.
-
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.
Application for use:
-
A new platform for drug-delivery, targeted to pathologies with high cathepsins activity.
-
A potential cancer immunotherapy solution
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.
