Enzymatically cleavable self-assembled nanoparticles for morphogen delivery
Inventors
Assignees
Publication Number
US-12208168-B2
Publication Date
2025-01-28
Expiration Date
2040-03-06
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Abstract
The present disclosure is directed to hybrid multifunctional macromers that can self-assemble to form nanoparticles for on-demand and targeted release of morphogens. Embodiments of the disclosure can include the hybrid multifunctional macromers and peptide sequences incorporated therein, self-assembled nanoparticles including the hybrid multifunctional macromers, methods for producing the hybrid multifunctional macromers and peptide sequences, and methods for treating a disease by the on-demand and targeted delivery of a compound using the hybrid multifunctional macromers.
Core Innovation
The invention provides hybrid multifunctional macromers capable of self-assembly into nanoparticles for the on-demand and targeted release of morphogens. These macromers are composed of defined regions: a cleavage site containing a first amino acid sequence that can be specifically cleaved by proteins such as plasmin or matrix metalloproteinases (MMPs); an assembly site with a second amino acid sequence prone to non-covalent interactions (such as pi-pi stacking) for the formation of higher order structures; and a solubility region composed of a water-soluble polymer. All regions are covalently linked, and additional features can include linkers, spacers, and endcaps to modulate macromer properties.
The invention addresses the problem of controlled morphogen release, particularly in tissue regeneration applications where existing metal or ceramic delivery systems present drawbacks such as the risk of bioaccumulation at injury sites. The background highlights the need for alternative delivery platforms that can be customized for both targeting and triggered release of compounds, thereby avoiding persistent material buildup and accommodating biological processes.
By designing the macromer with tailored cleavage sites, the nanoparticles respond to enzyme activity (e.g., from mesenchymal stem cells secreting plasmin or MMPs), enabling the site-specific release of therapeutic agents—such as morphogens—only when and where required. The invention includes not only the composition of these macromers and nanoparticles, but also methods for their chemical synthesis and use in disease treatment, offering a flexible, biocompatible, and non-bioaccumulating platform for compound delivery.
Claims Coverage
The patent has one independent claim that establishes several inventive features related to the method for forming a hybrid multifunctional macromer.
Method for forming a hybrid multifunctional macromer
The method comprises: - Synthesizing a backbone amino acid sequence by linking 4-26 amino acids, where the sequence includes a cleavage site cleavable by an enzyme. The cleavage site specifically includes KFYK (lysine-phenylalanine-tyrosine-lysine; SEQ ID NO: 2). - Synthesizing an assembly peptide by linking an assembly site to an amino acid side chain in the backbone sequence. - Attaching a solubility region to the assembly peptide, where the assembly site includes a second amino acid sequence with 2-8 amino acid residues, and the solubility region is a water-soluble polymer.
The independent claim centers on the synthesis method for a macromer comprising enzyme-cleavable, assembly, and solubility domains, each with defined sequence or chemical features—as applied in constructing hybrid multifunctional macromers for targeted compound delivery.
Stated Advantages
The invention provides improved biocompatibility compared to inorganic delivery vehicles.
The disclosed macromers and nanoparticles enable therapeutically efficacious treatments for applications such as promoting vascularized osteogenesis.
The system does not lead to bioaccumulation, thus avoiding persistent buildup of materials in the body at delivery sites.
Documented Applications
The on-demand and targeted delivery of morphogens for tissue regeneration, including the reconstruction of skeletal defects.
Methods for treating a disease by administering nanoparticles composed of the hybrid multifunctional macromer for the delivery of a compound (such as proteins like bone morphogenic protein).
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