	US 12,077,741 B2
	Crosslinked hydrogel compositions for regulating states of encapsulated cancer cells
John H. Slater, Landenberg, PA (US); Shantanu Pradhan, Chennai (IN); and Cindy Jazmin Farino Reyes, Claymont, DE (US)
Assigned to University Of Delaware, Newark, DE (US)
Filed by John H. Slater, Landenberg, PA (US); Shantanu Pradhan, Chennai (IN); and Cindy Jazmin Farino Reyes, Claymont, DE (US)
Filed on Jun. 4, 2020, as Appl. No. 16/893,330.
Application 16/893,330 is a continuation in part of application No. PCT/US2018/063787, filed on Dec. 4, 2018.
Claims priority of provisional application 62/594,077, filed on Dec. 4, 2017.
Prior Publication US 2020/0299627 A1, Sep. 24, 2020
Int. Cl. C12Q 1/37 (2006.01); C07K 5/11 (2006.01); C07K 5/113 (2006.01); C07K 7/06 (2006.01); C07K 7/08 (2006.01); C12M 1/12 (2006.01); C12N 5/09 (2010.01); G01N 1/30 (2006.01); G01N 21/64 (2006.01); G01N 33/50 (2006.01)

CPC C12M 25/00 (2013.01) [C07K 5/1019 (2013.01); C07K 5/1021 (2013.01); C07K 7/06 (2013.01); C07K 7/08 (2013.01); C12N 5/0693 (2013.01); G01N 1/30 (2013.01); G01N 21/6428 (2013.01); G01N 33/5011 (2013.01); G01N 33/5091 (2013.01); C12N 2503/00 (2013.01); C12N 2533/40 (2013.01); C12N 2533/50 (2013.01); G01N 2021/6439 (2013.01)]

25 Claims

1. A method of regulating a state of cancer cells, the method comprising:

i) providing a system comprising:

a) a crosslinked poly(ethylene glycol) (PEG)-based hydrogel composition comprising an acrylate-polymer-peptide macromer and a Type 1 ultraviolet (UV) photoinitiator, wherein the acrylate-polymer-peptide macromer comprises a first peptide and a first acrylate-PEG polymer covalently conjugated with the first peptide, wherein the first peptide consists of the sequence of X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11, and wherein each of the X1 to X11 is G, P, Q, W, I or K,

b) a cell culture medium in contact with the crosslinked PEG-based hydrogel composition, and

c) cancer cells in contact with the cell culture medium and encapsulated in the crosslinked PEG-based hydrogel composition, wherein the cancer cells are in cell restricted survival dormancy; and

ii) photopolymerizing a cell-adhesive macromer at 2-20 mM with the crosslinked PEG-based hydrogel composition, and thereby the cancer cells are induced to switch from the cell restricted survival dormancy to invasive growth,

wherein the cell-adhesive macromer comprises a cell-adhesive peptide and a second acrylate-poly(ethylene glycol) (PEG) covalently conjugated with the cell-adhesive peptide, wherein the cell-adhesive peptide comprises a second peptide selected from the group consisting of RGDS (SEQ ID NO: 4), RDGS (SEQ ID NO: 5), RGES (SEQ ID NO: 6), REGS (SEQ ID NO: 7), IKVAV (SEQ ID NO: 8), VVIAK (SEQ ID NO: 9), YIGSR (SEQ ID NO: 10), YSRIG (SEQ ID NO: 11), DGEA (SEQ ID NO: 12), DAEG (SEQ ID NO: 13), and combinations thereof.