Short Soluble Coumarin Crosslinkers for Light-Controlled Release of Cells and Proteins from Hydrogels.
Materials that degrade or dissociate in response to low power light promise to enable on-demand, precisely localized delivery of drugs or bioactive molecules in living systems. Such applications remain elusive because few materials respond to wavelengths that appreciably penetrate tissues. The photocage bromohydroxycoumarin (Bhc) is efficiently cleaved upon low-power ultraviolet (UV) and near-infrared (NIR) irradiation through one- or two-photon excitation, respectively. We have designed and synthesized a short Bhc-bearing crosslinker to create light-degradable hydrogels and nanogels. Our crosslinker breaks by intramolecular cyclization in a manner inspired by the naturally occurring ornithine lactamization, in response to UV and NIR light, enabling rapid degradation of polyacrylamide gels and release of small hydrophilic payloads such as an ∼10 nm model protein and murine mesenchymal stem cells, with no background leakage.
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Caroline
C
de Gracia Lux
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Jacques
J
Lux
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Guillaume
G
Collet
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Sha
S
He
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Minnie
M
Chan
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Jason
J
Olejniczak
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Alexandra
A
Foucault-Collet
Skaggs School of Pharmacy and Pharmaceutical Sciences, §Department of NanoEngineering, ‡Department of Chemistry and Biochemistry, and ∥Center for Excellence in Nanomedicine and Engineering, University of California at San Diego , 9500 Gilman Drive, La Jolla, California 92093-0600, United States.
Adah
A
Almutairi
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D008027:Light; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D011506:Proteins / Q000737:chemistry*; D012995:Solubility
D003374:Coumarins; D003432:Cross-Linking Reagents; D020100:Hydrogels; D011506:Proteins