Crosslinked DNA chains with hydrophilic polymeric networks in DNA hydrogel-based stimuli-responsive delivery systems are also widely investigated . DNA origami-based nanobricks of rectangular and tubular shapes with varied dimensions were utilized to deliver siRNA to anti-apoptotic protein Bcl2, in vitro and in vivo . It was demonstrated that the addition of a cationic polymer layer on a DNA nanoclew (NC) core, carrying Cas12a/CRISPR RNA (crRNA) ribonucleoprotein (RNP), not only made the nanomaterial surface, negatively charged under a physiological pH but also reverted to positive charge under an acidic environment and showed significantly reducing the expression of PCSK9 which resulted in cholesterol regulation . A tubular DNA origami nanodevice loaded by siRNA and doxorubicin was developed with additional components including tumor-penetrating ligands and stimuli-responsive DNA locks. These locks, containing disulfide bonds, kept the nanodevices closed until they encounter reducing agents like glutathione in tumor cells, triggering their opening and releasing the siRNA cargo. The nanodevice also incorporates cellpenetrating peptides to enhance cellular uptake. By targeting the key proteins involved in tumor progression, in vitro and in vivo experiments demonstrated effective gene silencing and combined cancer therapy at the tumor site .