Short Soluble Coumarin Crosslinkers for Light-Controlled Release of Cells and Proteins from Hydrogels

Abstract

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.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

“…Moreover, the uniqueness of each previously reported responsive platform necessitates a complete material redesign – one that is generally not synthetically tractable due to inherent constraints on material composition and vehicle geometry – in order to alter the response profiles or utilize different biochemical triggers. Further, the subset of degradable materials demonstrated for live cell release has been limited to single biological inputs 20 – 23 , confining next-generation cellular therapeutics to simple delivery platforms.…”

Active Regulation of On‐Demand Drug Delivery by Magnetically Triggerable Microspouters

“…Moreover, they have the advantages of being able to accommodate a large quantity of drug and achieve multiple dosing after a single administration through repeated triggering. Polymeric systems for triggerable drug delivery such as ferrogels, polyelectrolyte hydrogels, and light‐sensitive matrices have been studied. Drug release from these systems could be accelerated through mechanisms including ultrasound/light‐mediated degradation or electromagnetic field‐induced deformation of matrices .…”

Spatiotemporal hydrogel biomaterials for regenerative medicine

“…215 Hydrogels incorporating the coumarin functionality as a photolabile molecule have also been synthesized. 216,217 Coumarin photocleavable units are advantageous because of their greatly increased 2-photon uncaging cross section compared to the o NB group. 214 In one approach, researchers take advantage of the different spectral properties of some coumarin or nitrobenzyl species relative to each other.…”