Ultrasound-triggered drug delivery for glioma therapy through gambogic acid-loaded nanobubble-microbubble complexes

Biomedicine & Pharmacotherapy

Fei Yan¹  Nana Li²  Hongwei Wu³  Liansheng Chang⁴  Kang Guo⁵  Yongling Wang⁶  Xixi Wei⁶  Yaling Yin⁶  Lu Wang⁶  Yu Shi⁷  Feng Wang⁸  Lei Dong⁸  Yuqiao Chang⁸  Simin Liang⁹ 

[1] Correspondence to: Peking University Shenzhen Hospital, 1120 Lian-Hua Road, Shenzhen, Guangdong 518036, China.;CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan 453002, China;Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453002, China;Department of Oncology, The third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, China;Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China;Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen 518036, China;Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China;The Sixth Clinical Medical College, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Fu-tian), Shenzhen, Guangdong, China;

关键词: Focused ultrasound;    Blood–brain barrier;    Gambogic acid;    Glioma;   

DOI  :  

来源: DOAJ

【 摘 要 】

Glioma is one of the most common primary brain tumors. Gambogic acid (GA) is widely used in tumor chemotherapy. However, GA has poor water solubility, low bioavailability, and difficult permeability across the blood–brain barrier (BBB), leading to poor efficacy against brain tumors. In our study, we developed negatively charged GA-loaded PLGA nanobubbles [GA/poly(lactic-co-glycolic acid) (PLGA)] and conjugated them onto the surface of cationic lipid microbubbles (CMBs) through electrostatic interactions. The resulting GA/PLGA–CMB complex was characterized for its particle size, distribution, drug encapsulation efficiency, and ultrasound imaging property, revealing a high drug encapsulation efficiency and excellent contrast imaging capability. Importantly, significantly enhanced GA delivery into the brain could be observed after the intravenous administration of GA/PLGA–CMBs combined with low-intensity focused ultrasound (FUS) due to the cavitation from CMBs, which mediated blood–brain barrier (BBB) opening. Taking advantage of the opened BBB, GA/PLGA nanobubbles could be delivered into the tumor. Then, the second FUS irradiation at higher energy was used to induce the cavitation of GA/PLGA nanobubbles, producing the second cavitation on tumor cells, significantly enhancing the ability of GA to enter tumor cells and inhibit tumor growth inhibition efficacy.

【 授权许可】

Unknown