Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus Delivery

International Journal of Molecular Sciences

Li-Fang Jin¹  Fan Li¹  Hui-Ping Wang²  Fang Wei²  Peng Qin³ 

[1] Department of Ultrasound, Shanghai Jiaotong University Affiliated First People’s Hospital, 100 Haining Road, Shanghai 200080, China; E-Mails:;Experimental Research Center, Shanghai Jiaotong University Affiliated First People’s Hospital, 100 Haining Road, Shanghai 200080, China; E-Mails:;Department of Instrumentation Science and Engineering, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China; E-Mail:

关键词: ultrasound;    microbubbles;    endocytosis;    adeno-associated virus;    sonoporation;   

DOI  :  10.3390/ijms14059737

来源: mdpi

【 摘 要 】

The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD) to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV) into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM) revealed that UTMD stimulated formation of clathrin-coated pits (CPs) and uncoated pits (nCPs). Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland