TY - JOUR
T1 - Allosteric DNA Nanorobots for Targeted Glioma Therapy
T2 - Acid-Triggered Doxorubicin Delivery
AU - Liu, Fengyu
AU - Dong, Lixin
AU - Huang, Qiang
AU - Shi, Qing
AU - Arai, Tatsuo
AU - Fukuda, Toshio
AU - Liu, Xiaoming
N1 - Publisher Copyright:
© 2026 Wiley-VCH GmbH.
PY - 2026/5/4
Y1 - 2026/5/4
N2 - Chemotherapy remains the primary therapeutic option for glioma treatment due to its noninvasive nature and broad applicability. However, most existing chemotherapeutic carriers suffer from poor blood-brain barrier (BBB) permeability and undefined drug delivery mechanisms, limiting their effectiveness in brain tumor therapy. Here, we present an allosteric DNA nanorobot for targeted glioma therapy, engineered via DNA origami for acid-triggered doxorubicin (Dox) delivery. This nanorobot features cytosine-rich pH sensors that facilitate its assembly into a stable tetrahedral configuration, crucial for efficient BBB traversal. Striking in vitro and in vivo studies demonstrate that these Dox-loaded nanorobots not only effectively cross the BBB but also accumulate in glioma tissues, resulting in significant suppression of tumor growth. We decode the drug delivery mechanism: acid-induced destabilization of DNA nanorobots triggers Dox release with optimal bioavailability. This pioneering nanorobot, powered by pH-responsive allosteric dynamics, enables revolutionary precision glioma therapy.
AB - Chemotherapy remains the primary therapeutic option for glioma treatment due to its noninvasive nature and broad applicability. However, most existing chemotherapeutic carriers suffer from poor blood-brain barrier (BBB) permeability and undefined drug delivery mechanisms, limiting their effectiveness in brain tumor therapy. Here, we present an allosteric DNA nanorobot for targeted glioma therapy, engineered via DNA origami for acid-triggered doxorubicin (Dox) delivery. This nanorobot features cytosine-rich pH sensors that facilitate its assembly into a stable tetrahedral configuration, crucial for efficient BBB traversal. Striking in vitro and in vivo studies demonstrate that these Dox-loaded nanorobots not only effectively cross the BBB but also accumulate in glioma tissues, resulting in significant suppression of tumor growth. We decode the drug delivery mechanism: acid-induced destabilization of DNA nanorobots triggers Dox release with optimal bioavailability. This pioneering nanorobot, powered by pH-responsive allosteric dynamics, enables revolutionary precision glioma therapy.
KW - DNA nanorobot
KW - blood-brain barrier
KW - glioma
KW - molecular dynamics simulation
UR - https://www.scopus.com/pages/publications/105029167606
U2 - 10.1002/adfm.202527455
DO - 10.1002/adfm.202527455
M3 - Article
AN - SCOPUS:105029167606
SN - 1616-301X
VL - 36
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 36
M1 - e27455
ER -