DNA-triggered activation of aptamer-neutralized enzyme for <i>in situ</i> formation of injectable hydrogel

Injectable hydrogels have been widely studied for the embolization of vascular malformations and the control of bleeding in hemorrhages. An ideal injectable hydrogel in these applications needs to form once contacting with the blood components, which enables easy control of hydrogel formation and injectability. However, this type of injectable hydrogel has not yet been widely studied. In this work, an injectable hydrogel system was developed by using a bispecific aptamer-neutralized enzyme and a triggering DNA. The results show that the system remained in its solution or pre-gelation state in the presence of the bispecific aptamer. Upon contact with the triggering DNA, the system was transformed into a hydrogel state. <i>In vitro</i> aneurysm and endovascular embolization were further conducted, and the results showed the DNA administered out of the hydrogel system could trigger the activation of aptamer-bound enzymes for the accelerated formation of the injectable hydrogel. Therefore, this study has successfully demonstrated that a bispecific aptamer-neutralized enzyme in the pre-gelation system can be rapidly released to accelerate the formation of injectable hydrogels when the system is in contact with the blood that contains a triggering DNA.