Crosslinked hydrogel compositions for regulating states of encapsulated cancer cells
Inventors
Slater, John H. • Pradhan, Shantanu • Farino Reyes, Cindy Jazmin
Assignees
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Publication Number
US-12077741-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The present invention discloses crosslinked poly(alkylene glycol) (PAG)-based hydrogel compositions, systems containing a plurality of cancer cells in contact with a cell culture media and encapsulated in the crosslinked PAG-based hydrogel composition and methods of making such crosslinked hydrogel compositions and systems. Also disclosed herein are methods of using such compositions and systems, such as, for example for screening an agent for effectiveness of the agent against cancer cells. Also disclosed herein are kits containing one or more components including one or more systems of the present disclosure and one or more instructions.
Core Innovation
The invention provides a system for regulating a state of cancer cells. The system includes a crosslinked poly(ethylene glycol) (PEG)-based hydrogel composition comprising an acrylate-polymer-peptide macromer and a Type 1 ultraviolet (UV) photoinitiator. The acrylate-polymer-peptide macromer includes a first peptide and a first acrylate-PEG polymer covalently conjugated with the first peptide.
Cancer cells are encapsulated in the crosslinked PEG-based hydrogel composition and are in cell restricted survival dormancy while in contact with the cell culture medium. The method includes photopolymerizing a cell-adhesive macromer at 2-20 mM with the crosslinked PEG-based hydrogel composition. As a result, the cancer cells are induced to switch from the cell restricted survival dormancy to invasive growth.
The cell-adhesive macromer comprises a cell-adhesive peptide and a second acrylate-poly(ethylene glycol) (PEG) covalently conjugated with the cell-adhesive peptide. The cell-adhesive peptide comprises a second peptide selected from RGDS, RDGS, RGES, REGS, IKVAV, VVIAK, YIGSR, YSRIG, DGEA, DAEG, or combinations thereof.
Claims Coverage
The provided partial content includes one independent claim describing a method that uses a crosslinked Type 1 UV-crosslinked PEG-based hydrogel system to encapsulate cancer cells in cell restricted survival dormancy and then induces a switch to invasive growth by photopolymerizing a cell-adhesive macromer.
Type 1 UV-crosslinked PEG hydrogel with acrylate-polymer-peptide macromer
A crosslinked PEG-based hydrogel composition comprising an acrylate-polymer-peptide macromer and a Type 1 ultraviolet (UV) photoinitiator, where the acrylate-polymer-peptide macromer comprises a first peptide and a first acrylate-PEG polymer covalently conjugated with the first peptide.
Encapsulation of cancer cells in cell restricted survival dormancy
Cancer cells are in cell restricted survival dormancy when encapsulated in the crosslinked PEG-based hydrogel composition in contact with a cell culture medium.
Photopolymerizing a cell-adhesive macromer to induce switching to invasive growth
Photopolymerizing a cell-adhesive macromer at 2-20 mM with the crosslinked PEG-based hydrogel composition to induce the cancer cells to switch from cell restricted survival dormancy to invasive growth.
Cell-adhesive macromer with acrylate-PEG covalently conjugated to cell-adhesive peptide
The cell-adhesive macromer comprises a cell-adhesive peptide and a second acrylate-poly(ethylene glycol) (PEG) covalently conjugated with the cell-adhesive peptide.
The independent claim’s coverage centers on regulating cancer cell state by encapsulating cancer cells in cell restricted survival dormancy within a Type 1 UV photoinitiator-containing crosslinked PEG hydrogel, and then inducing a switch to invasive growth through photopolymerization of a cell-adhesive macromer.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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