Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma.
Overview
- Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China
- Center for Lab Teaching, School of Basic Medical Sciences, Wuhan University, Wuhan, China
- Department of Anatomy and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
- Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
- Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China
Abstract
Glioblastoma (GBM), the deadliest primary brain malignancy, resists treatment because of the blood‒brain barrier (BBB) and intrinsic resistance mechanisms. Fluorescein (FL), a clinically approved fluorophore, shows promise as a sonosensitizer for sonodynamic therapy (SDT), but faces challenges in tumor delivery and incomplete mechanistic understanding beyond ROS-mediated damage. We developed a bioinspired platelet-based delivery platform exploiting the natural tumor-homing properties of platelets for targeted FL delivery. Platelets were loaded with fluorescein diacetate (FDA), a lipophilic prodrug that is converted intracellularly to active FL, combined with probenecid to inhibit MRP1-mediated efflux, generating the ultrasound-responsive vitro, FL demonstrated sonocytotoxicity; upon low-intensity ultrasound, rapidly released FL into GBM cells, producing significant cytotoxicity enhanced by probenecid-mediated retention. In subcutaneous and orthotopic mouse models, intravenous with probenecid and sequential ultrasound achieved extensive tumor FL accumulation, massive necrosis, significant growth inhibition, and prolonged survival. Mechanistically, FL-SDT induces DNA damage while promoting HIF-1α degradation via the ubiquitin‒proteasome and autophagy‒lysosome pathways, thus suppressing downstream DNA repair enzymes (SMUG1 and LIG4). This dual mechanism combines direct genotoxicity with impaired DNA repair capacity, underlying the potent anti-GBM efficacy. Our platelet-based FL delivery represents a practical, safe, translational therapy for overcoming BBB limitations by disabling HIF-1α-regulated DNA repair
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Datasets cited
- figshare:33112621, at figshare; found in DataCite
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 5 keywords, 14 MeSH terms, 2 funders, 47 references.
Cite
This paper
Guo, Y.-X., Deng, Q., Li, K., Zhang, Q., Guo, J., Wang, M.-F., Wu, J.-L., Lei, H.-M., Chen, Y.-Y., Pu, H., Gao, Y.-f., Xu, Y.-H., Chen, X., & Zhou, Q. (2026). Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma. Drug delivery, 33(1), 2708389. https://
BibTeX
@article{guo2026ultrasou
author = {Guo, Yu-Xin and Deng, Qing and Li, Ke and Zhang, Quan and Guo, Jie and Wang, Meng-Fei and Wu, Jia-Lin and Lei, Hui-Mei and Chen, Yue-Ying and Pu, Huan and Gao, Yu-fan and Xu, Yong-Hong and Chen, Xiao and Zhou, Qing},
title = {{Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma}},
journal = {Drug delivery},
year = {2026},
month = jul,
volume = {33},
number = {1},
pages = {2708389},
publisher = {Taylor \& Francis},
issn = {1071-7544},
doi = {10.1080/
url = {https://
pmid = {42523098},
pmcid = {PMC13421115}
}
RIS
TY - JOUR
AU - Guo, Yu-Xin
AU - Deng, Qing
AU - Li, Ke
AU - Zhang, Quan
AU - Guo, Jie
AU - Wang, Meng-Fei
AU - Wu, Jia-Lin
AU - Lei, Hui-Mei
AU - Chen, Yue-Ying
AU - Pu, Huan
AU - Gao, Yu-fan
AU - Xu, Yong-Hong
AU - Chen, Xiao
AU - Zhou, Qing
TI - Ultrasound-triggered platelet vehicles loading fluorescein for targeted sonodynamic therapy of glioblastoma
T2 - Drug delivery
J2 - Drug Deliv
PY - 2026
DA - 2026/
VL - 33
IS - 1
SP - 2708389
SN - 1071-7544
PB - Taylor & Francis
DO - 10.1080/
UR - https://
LA - en
ER -
CSL-JSON
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