Albumin-Phthalocyanine Supramolecular Complex Shows Favorable Blood-Brain Barrier Penetration and Enhanced Sonodynamic Therapy for Gliomas

Abstract

The high penetration depth of sonodynamic therapy (SDT) and the instantaneous opening of the blood–brain barrier (BBB) due to ultrasound stimulation make SDT superior for treating gliomas. Here, we construct amphiphilic cationic phthalocyanine (ZnPc) and combine it with human serum albumin (HSA) to create a ZnPc–HSA supramolecular complex through green synthesis. The urgent need for energy to achieve rapid tumor growth and the strong expression of the albumin binding-related protein gives ZnPc–HSA the ability to cross the BBB and enrich gliomas. Moreover, this complex increases the biocompatibility and penetration depth (by approximately 1.75 times) and enhances reactive oxygen species generation (by approximately 16.54 times) after ultrasound stimulation. Further, ZnPc–HSA-based SDT effectively inhibits the growth of gliomas in diseased mice and prolongs their lifetime. This study provides a promising platform for future construction of supramolecular biomimetic nanomaterials for SDT to treat brain disorders.

Note:
Funding Declaration: Rui Wang thanks the supporting from the Hainan Provincial Natural Science Foundation of China (grant No. 823MS050) and the supporting from the Education Department of Hainan Province, project number: Hnky2023ZD-11. Xingshu Li thanks the National Natural Science Foundation of China (grant No. 22078066). Fabiao Yu thanks the National Natural Science Foundation of China (Grant No. 22264013) and the Hainan Province Science and Technology Special Fund (Grant ZDYF2020133) funded by Hainan Province Clinical Medical Center (2021). Dokyoung Kim thanks the Core Research Institute (CRI) Program, the Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Education (NRF 2018-R1A6A1A03025124) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI21C0239). Juyoung Yoon thanks to the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1A2C3005420).

Conflicts of Interest: None

Ethical Approval: Animal treatment and maintenance were performed according to the Animal Care and Use Guidelines by Kyung Hee University. All experimental protocols were approved by the Institutional Animal Care and Use Committee of Kyung Hee University (Approval number: KHSASP-21-305).

Keywords: sonodynamic therapy, phthalocyanine supramolecular complex, blood-brain barrier penetration, Glioma