Enzymatically Cleavable Self Assembled Nanoparticles for Morphogen Delivery


Reference #: 01350

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There is a continuing need to develop approaches for controlled release of morphogens, which control cell shape, in applications such as tissue regeneration. While metal and ceramic particles have been used as delivery systems, these materials can have drawbacks because even though they are biocompatible, there is a risk for accumulation in the body, something that may be a particular issue when the site of delivery is already damaged by an injury. Needed in the art are alternative delivery systems that can be functionalized in various ways to both target and trigger release of a compound without leading to bioaccumulation.

Invention Description:

Smart nanoparticles (NPs) that respond to their microenvironment to release an attached cargo are ideal for the delivery of morphogenetic factors. In that regard, short peptides have been used to assemble hydrophilic macromers into nanoparticles, because of their tendency to dissolve in water. Hydrophilic NPs are ideal as a matrix for the delivery of proteins because their hydrophilic nature prevents protein denaturation. Further, NPs in the size range of 50 to 500 nm can be mixed with a precursor solution and injected in minimally invasive procedures. Furthermore, protein retention in the site of the application is sharply increased by conjugation or attachment to NPs in the 50-500 nm size range. In addition, NPs that are self-assembled using short peptide sequences possess high biocompatibility and they are amenable to surface modification. Further, NPs assembled with short peptide sequences have a narrower size range and well-defined geometries compared to those assembled using non-peptide hydrophobic segments. 

Potential Applications:

In many medical applications, peptides, proteins, morphogens, cytokines, and growth factors need to be released locally in response to progenitor cells invading the tissue. Specifically, in regenerative medicine, biologically active agents like morphogens need to be released to induce differentiation of different cell types to specific lineage or to stimulate their maturation to different phenotypes.

Advantages and Benefits:

The advantages of this invention are the amphiphilic nature of the self-assembled NPs (hydrophilic PEG, hydrophobic phenylalanine sequence, and the amphiphilic LFTK) prevents denaturation of the grafted protein. Also, the short PEG macromer is inert and the short self-assembling peptide and short plasmin-cleavable peptide are non-immunogenic and the macromer is excreted or resorbed through metabolic pathways. The nanoparticle nature of the delivery system allows injection for minimally invasive procedures and the nanoscale size prevents diffusion of the protein away from the site of application for higher efficacy and bioavailability. The protein is released on-demand as the migrating cells secrete enzymes to cleave the cleavable peptide. Protein release is independent of the size of shape of the protein and any protein can be released in a cell responsive manner.

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Enzymatically Cleavable Self Assembled Nanoparticles for Morphogen Delivery Utility United States 16/811,023 11,672,767 3/6/2020 6/13/2023   Published
For Information, Contact:
Technology Commercialization
University of South Carolina
Esmaiel Jabbari
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