Dadhwal Sumit, Fairhall Jessica M, Hook Sarah, Gamble Allan B
School of Pharmacy, University of Otago Dunedin 9054 New Zealand
RSC Adv. 2020 Mar 3;10(16):9234-9244. doi: 10.1039/d0ra01013h. eCollection 2020 Mar 2.
The synthesis of a bioorthogonal-responsive low molecular weight diphenylalanine (PhePhe)-based hydrogel that is capped with a 4-azido-2,3,5,6-tetrafluorobenzyl carbamate self-immolative linker is reported. The hydrogelator (AzF-PhePhe) generates a stable hydrogel at 0.1 wt%, and rapidly reacts with the bioorthogonal reagent -cyclooctene (TCO), inducing a gel-to-solution transition. The critical gel concentration is five-fold lower than our previously synthesized non-fluorinated hydrogelator (Az-PhePhe), and the minimum concentration of TCO required for visible gel-to-solution transition in 24 hours is 1 mM. Doxorubicin can be encapsulated in the hydrogel and TCO-triggered dissolution results in 76% and 89% release after 10 and 24 hours, respectively. Compared with our non-substituted aryl azide capping group used for Az-PhePhe, the tetrafluorinated aryl azide group improves the stability of the hydrogel in unbuffered water at a lower critical gel concentration, while improving sensitivity towards the bioorthogonal reagent TCO.
报道了一种生物正交响应性低分子量基于二苯丙氨酸（PhePhe）的水凝胶的合成，该水凝胶用4-叠氮基-2,3,5,6-四氟苄基氨基甲酸酯自牺牲连接基团封端。水凝胶剂（AzF-PhePhe）在0.1 wt%时形成稳定的水凝胶，并与生物正交试剂反式环辛烯（TCO）快速反应，引发凝胶-溶液转变。临界凝胶浓度比我们之前合成的非氟化水凝胶剂（Az-PhePhe）低五倍，24小时内可见凝胶-溶液转变所需的TCO最低浓度为1 mM。阿霉素可封装在水凝胶中，TCO触发的溶解分别在10小时和24小时后导致76%和89%的释放。与我们用于Az-PhePhe的未取代芳基叠氮封端基团相比，四氟芳基叠氮基团在较低的临界凝胶浓度下提高了水凝胶在无缓冲水中的稳定性，同时提高了对生物正交试剂TCO的敏感性。
