Folate-Targeted polymeric micelles enhance the anti-glioma efficacy of pterostilbene in an orthotopic rat model
7 affiliations
- 1College of Pharmacy & Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, China
- 2Second Affiliated Hospital, Dalian Medical University, Dalian, 116044, China
- 3The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
- 4College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
- 5Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA
- 6College of Pharmacy & Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, China; The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China; Corresponding authors
- 7College of Pharmacy & Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, China; Corresponding authors
Abstract
The clinical translation of Pterostilbene, a neuroactive stilbene with broad therapeutic potential, is hampered by its poor aqueous solubility and insufficient brain accumulation. To address these limitations, we developed a folate receptor-targeted polymeric micelle system (F–Pt/M) using poly (ethylene glycol)-block-poly (ε-caprolactone) copolymers. The optimized F–Pt/M exhibited a small hydrodynamic diameter (∼133 nm), high drug loading, and increased the apparent solubility of pterostilbene by 25-fold. In folate receptor-expressing U251 and RG-2 glioma cells, F–Pt/M significantly enhanced cellular uptake via folate-mediated endocytosis and showed superior cytotoxicity compared to non-targeted micelles. In an orthotopic RG-2 glioma model, intravenous administration of F–Pt/M improved brain accumulation and prolonged median survival by 76.5% relative to free drug. Mechanistically, the enhanced anti-glioma efficacy was associated with induction of apoptosis and inhibition of the STAT3 signaling pathway. These findings establish folate-targeted micelles as a robust and versatile nanoplatform for delivering poorly soluble bioactive compounds to the brain, with pterostilbene representing a promising candidate for further neuro-oncological development.
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BibTeX
@article{yang2026folatetargeted,
title = {{Folate-Targeted polymeric micelles enhance the anti-glioma efficacy of pterostilbene in an orthotopic rat model}},
author = {Xiaobo Yang and Yuze Sun and Huan Jin and Hailin Zhou and Yunqiao Yang and Yanan Su and Jinan Wang and Zhiwei Zhao and Wenyao Yu and Moli Wu and Qian Wang and Conghongting Liu and Wen Sun and Changyuan Wang and Chong Wang and Li Lv and Mingzhan Li and Jing Ning and Brant E. Isakson and Yinan Wang and Xiaohong Shu},
journal = {Neurotherapeutics},
year = {2026},
month = oct,
doi = {10.1016/j.neurot.2026.e01078},
url = {https://doi.org/10.1016/j.neurot.2026.e01078},
note = {CC BY},
}
RIS
TY - JOUR
TI - Folate-Targeted polymeric micelles enhance the anti-glioma efficacy of pterostilbene in an orthotopic rat model
AU - Xiaobo Yang
AU - Yuze Sun
AU - Huan Jin
AU - Hailin Zhou
AU - Yunqiao Yang
AU - Yanan Su
AU - Jinan Wang
AU - Zhiwei Zhao
AU - Wenyao Yu
AU - Moli Wu
AU - Qian Wang
AU - Conghongting Liu
AU - Wen Sun
AU - Changyuan Wang
AU - Chong Wang
AU - Li Lv
AU - Mingzhan Li
AU - Jing Ning
AU - Brant E. Isakson
AU - Yinan Wang
AU - Xiaohong Shu
PY - 2026
DA - 2026/10/24
JO - Neurotherapeutics
DO - 10.1016/j.neurot.2026.e01078
UR - https://doi.org/10.1016/j.neurot.2026.e01078
AB - The clinical translation of Pterostilbene, a neuroactive stilbene with broad therapeutic potential, is hampered by its poor aqueous solubility and insufficient brain accumulation. To address these limitations, we developed a folate receptor-targeted polymeric micelle system (F–Pt/M) using poly (ethylene glycol)-block-poly (ε-caprolactone) copolymers. The optimized F–Pt/M exhibited a small hydrodynamic diameter (∼133 nm), high drug loading, and increased the apparent solubility of pterostilbene by 25-fold. In folate receptor-expressing U251 and RG-2 glioma cells, F–Pt/M significantly enhanced cellular uptake via folate-mediated endocytosis and showed superior cytotoxicity compared to non-targeted micelles. In an orthotopic RG-2 glioma model, intravenous administration of F–Pt/M improved brain accumulation and prolonged median survival by 76.5% relative to free drug. Mechanistically, the enhanced anti-glioma efficacy was associated with induction of apoptosis and inhibition of the STAT3 signaling pathway. These findings establish folate-targeted micelles as a robust and versatile nanoplatform for delivering poorly soluble bioactive compounds to the brain, with pterostilbene representing a promising candidate for further neuro-oncological development.
SN - 1878-7479
SN - 1933-7213
ER -