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NHC Key Laboratory of Tropical Disease Control, Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou 571199, China
bFujian Provincial Key Laboratory for Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350108, China
cDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea
dDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
eCollege of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China
fGradutate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
Received 2 April 2026, Revised 10 June 2026, Accepted 18 June 2026, Available online 19 June 2026, Version of Record 23 June 2026.
Sensors and Actuators B: ChemicalVolume 467, Part 2, 15 November 2026, 140389
https://doi.org/10.1016/j.snb.2026.140389
Highlights•A biomimetic ZnPc–HSA complex is formed by green self-assembly.
•ZnPc–HSA enables BBB crossing and NIR-guided glioma imaging.
•HSA complexation boosts ultrasound-triggered ROS beyond dispersion effects.
•ZnPc–HSA improves tumor penetration and sonodynamic efficacy.
Abstract
Sonodynamic therapy (SDT) is highly attractive for glioma treatment owing to its deep tissue penetration and the ultrasound-triggered transient opening of the blood–brain barrier (BBB). Herein, we report a biomimetic supramolecular strategy that integrates an amphiphilic cationic zinc phthalocyanine (ZnPc) with human serum albumin (HSA) via a green self-assembly process, yielding ZnPc–HSA. Benefiting from tumor metabolic demand and secreted protein acidic and rich in cysteine-mediated albumin uptake, the complex efficiently crosses the BBB and preferentially accumulates in orthotopic gliomas, thus enabling it to be monitored by its inherent near-infrared (NIR) fluorescence. Importantly, supramolecular complexation with HSA unexpectedly and significantly potentiates the sonodynamic activity of ZnPc, an effect that cannot be attributed solely to improved dispersibility. Moreover, compared with the control group, the ZnPc–HSA complex showed enhanced biocompatibility, deeper tumor penetration (∼1.75 times), and a significant increase in reactive oxygen species generation under ultrasound irradiation (∼16.54 times). Consequently, NIR fluorescence–guided SDT based on ZnPc–HSA effectively suppresses glioma growth and significantly prolongs survival in orthotopic mouse models. This work establishes a versatile supramolecular biomimetic platform that integrates BBB penetration, imaging guidance, and amplified sonodynamic efficacy, offering a generalizable strategy for SDT-based treatment of brain disorders.

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