Therapeutic Peptide-Programmed Liquid-Crystalline Topology Switching for pH-Gated Postoperative Cancer Immunotherapy.
- 1School of Pharmacy and Laboratory of Drug Discovery from Natural Resources and Industrialization, Macau University of Science and Technology, Macau, China.
- 2Livzon Pharmaceutical Group Inc., National Engineering Research Center of Microsphere Technology for Controlled-Release Drug Delivery, Zhuhai, China.
- 3Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Abstract
Stimuli-responsive depots for postoperative cancer therapy often treat therapeutic payloads as passive cargo, resulting in premature leakage and limited on-demand activation. Herein, we report a therapeutic peptide-programmed liquid-crystalline depot in which the Vpr-derived antitumor peptide (VDAP) functions simultaneously as an immunotherapeutic effector and a supramolecular topology regulator. At physiological pH, cationic α-helical VDAP was electrostatically anchored by oleic acid-containing lipid domains, reinforcing a compact inverse hexagonal (HII) topology associated with reduced peptide diffusion. In the acidic postoperative tumor microenvironment, protonation of oleic acid could disrupt anionic anchoring, whereas histidine protonation within VDAP amplified intrachannel electrostatic repulsion. This cooperative peptide-lipid charge reprogramming could drive graded liquid-crystalline topology remodeling from a diffusion-restrictive HII organization to a more interconnected bicontinuous cubic Im3̄m network, consistent with increased pH-responsive peptide release. In an orthotopic incomplete-resection breast tumor model, the depot induced immunogenic tumor destruction, enhanced damage-associated molecular pattern release, promoted dendritic cell maturation and CD8⁺ T cell infiltration, and reshaped the immunosuppressive surgical bed. These results demonstrate that electrostatic-topology-gated VDAP-enabled supramolecular topology switching provides effective adaptive local cancer immunotherapy, effectively suppressing postoperative tumor recurrence and attenuating pulmonary metastasis.
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BibTeX
@article{yan2026therapeutic,
title = {{Therapeutic Peptide-Programmed Liquid-Crystalline Topology Switching for pH-Gated Postoperative Cancer Immunotherapy.}},
author = {Yan Yan and Bin Chen and Yanqing Wang and Yuxi Hou and Zhenlin Ma and Zini Yang and Xia Yin and Yiling Chen and Litao Huang and Menghan Cai and Xinlin Liu and Yi Zhun Zhu and Li Ye},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78360},
url = {https://europepmc.org/article/MED/42893475},
note = {CC BY},
}
RIS
TY - JOUR
TI - Therapeutic Peptide-Programmed Liquid-Crystalline Topology Switching for pH-Gated Postoperative Cancer Immunotherapy.
AU - Yan Yan
AU - Bin Chen
AU - Yanqing Wang
AU - Yuxi Hou
AU - Zhenlin Ma
AU - Zini Yang
AU - Xia Yin
AU - Yiling Chen
AU - Litao Huang
AU - Menghan Cai
AU - Xinlin Liu
AU - Yi Zhun Zhu
AU - Li Ye
PY - 2026
DA - 2026/10/18
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78360
UR - https://europepmc.org/article/MED/42893475
AB - Stimuli-responsive depots for postoperative cancer therapy often treat therapeutic payloads as passive cargo, resulting in premature leakage and limited on-demand activation. Herein, we report a therapeutic peptide-programmed liquid-crystalline depot in which the Vpr-derived antitumor peptide (VDAP) functions simultaneously as an immunotherapeutic effector and a supramolecular topology regulator. At physiological pH, cationic α-helical VDAP was electrostatically anchored by oleic acid-containing lipid domains, reinforcing a compact inverse hexagonal (HII) topology associated with reduced peptide diffusion. In the acidic postoperative tumor microenvironment, protonation of oleic acid could disrupt anionic anchoring, whereas histidine protonation within VDAP amplified intrachannel electrostatic repulsion. This cooperative peptide-lipid charge reprogramming could drive graded liquid-crystalline topology remodeling from a diffusion-restrictive HII organization to a more interconnected bicontinuous cubic Im3̄m network, consistent with increased pH-responsive peptide release. In an orthotopic incomplete-resection breast tumor model, the depot induced immunogenic tumor destruction, enhanced damage-associated molecular pattern release, promoted dendritic cell maturation and CD8⁺ T cell infiltration, and reshaped the immunosuppressive surgical bed. These results demonstrate that electrostatic-topology-gated VDAP-enabled supramolecular topology switching provides effective adaptive local cancer immunotherapy, effectively suppressing postoperative tumor recurrence and attenuating pulmonary metastasis.
SN - 2198-3844
ER -