Lei Dong,1,* Nana Li,1,* Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound
