Chemically programmable hybrid membrane-camouflaged acetate gossypol prodrug reprograms the hepatic microenvironment for the treatment of liver fibrosis
5 affiliations
- 1School of Pharmacy, The Third Affiliated Hospital, Anhui Medical University, Hefei, 230032 Anhui China
- 2School of Pharmacy, Anhui Medical University, Hefei, 230032 Anhui China
- 3The Third Affiliated Hospital, Anhui Medical University, Hefei, 230032 Anhui China
- 4Research and Industrialization of New Drug Release Technology Joint Laboratory of Anhui Province, Hefei, 230032 Anhui China
- 5Department of pharmacy, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230032 Anhui China
Abstract
Background: Liver fibrosis represents a critical pathological process in chronic liver disease for which precision therapies remain limited.
Results: Here we report a biomimetic nanodrug (RAET NPs) that integrates a reactive oxygen species (ROS)-responsive prodrug of acetate gossypol with hybrid cell membrane camouflage and aptamer-mediated targeting. RAET NPs are constructed through modular assembly: the ROS-responsive prodrug core is encapsulated within a hybrid membrane shell formed by fusing activated hepatic stellate cell (HSC)-derived exosome membranes with M1-type macrophage membranes, followed by decoration with CD44-specific nucleic acid aptamers. This design preserves the full repertoire of membrane-associated targeting proteins while incorporating synthetic aptamers for enhanced recognition specificity. Meanwhile, RAET NPs remain in an inert state under normal physiological conditions to reduce biotoxicity and are converted into active drugs only in the fibrosis-induced reactive oxygen species (ROS)-rich microenvironment, enabling controlled drug release at the lesion site. In both organoid and animal models of liver fibrosis, RAET NPs suppress HSC activation and extracellular matrix deposition, significantly attenuating disease progression.
Conclusions: This biomimetic nanomedicine offers a novel strategy for precision treatment of liver fibrosis through the synergistic function of prodrug and biomimetic delivery.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04878-1.
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BibTeX
@article{song2026chemically,
title = {{Chemically programmable hybrid membrane-camouflaged acetate gossypol prodrug reprograms the hepatic microenvironment for the treatment of liver fibrosis}},
author = {Mingming Song and Ying Fang and Xiaqing Gong and Jiandong Wang and Han Yuan and Kai Wang and Xiaowen Yu and Jihui Tang},
journal = {Journal of Nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04878-1},
url = {https://doi.org/10.1186/s12951-026-04878-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Chemically programmable hybrid membrane-camouflaged acetate gossypol prodrug reprograms the hepatic microenvironment for the treatment of liver fibrosis
AU - Mingming Song
AU - Ying Fang
AU - Xiaqing Gong
AU - Jiandong Wang
AU - Han Yuan
AU - Kai Wang
AU - Xiaowen Yu
AU - Jihui Tang
PY - 2026
DA - 2026/07/01
JO - Journal of Nanobiotechnology
DO - 10.1186/s12951-026-04878-1
UR - https://doi.org/10.1186/s12951-026-04878-1
AB - Background: Liver fibrosis represents a critical pathological process in chronic liver disease for which precision therapies remain limited. Results: Here we report a biomimetic nanodrug (RAET NPs) that integrates a reactive oxygen species (ROS)-responsive prodrug of acetate gossypol with hybrid cell membrane camouflage and aptamer-mediated targeting. RAET NPs are constructed through modular assembly: the ROS-responsive prodrug core is encapsulated within a hybrid membrane shell formed by fusing activated hepatic stellate cell (HSC)-derived exosome membranes with M1-type macrophage membranes, followed by decoration with CD44-specific nucleic acid aptamers. This design preserves the full repertoire of membrane-associated targeting proteins while incorporating synthetic aptamers for enhanced recognition specificity. Meanwhile, RAET NPs remain in an inert state under normal physiological conditions to reduce biotoxicity and are converted into active drugs only in the fibrosis-induced reactive oxygen species (ROS)-rich microenvironment, enabling controlled drug release at the lesion site. In both organoid and animal models of liver fibrosis, RAET NPs suppress HSC activation and extracellular matrix deposition, significantly attenuating disease progression. Conclusions: This biomimetic nanomedicine offers a novel strategy for precision treatment of liver fibrosis through the synergistic function of prodrug and biomimetic delivery. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04878-1.
SN - 1477-3155
ER -