Development of exosome membrane materialsfused microbubbles for enhanced stability and efficient drug delivery of ultrasound contrast agent  

作　　者：Yongho Jang Jeehun Park Pilsu Kim Eun-Joo Park Hyungjin Sun Yujin Baek Jaehun Jung Tai-kyong Song Junsang Doh Hyuncheol Kim 

机构地区：[1]Department of Chemical and Biomolecular Engineering,Sogang University,Seoul 04107,Republic of Korea [2]Research Institute of Advanced Materials(RIAM),Institute of Engineering Research,Seoul National University,Seoul 08826,Republic of Korea [3]Department of Electronic Engineering,Sogang University,Seoul 04107,Republic of Korea [4]Biomedical Research Institute&Department of Radiology,Seoul National University Hospital,Seoul 03080,Republic of Korea [5]Interdisciplinary Program in Bioengineering,Seoul National University,Seoul 08826,Republic of Korea [6]Department of Materials Science and Engineering,Seoul National University,Seoul 08826,Republic of Korea [7]Institute of Engineering Research,Bio-MAX Institute,Seoul National University,Seoul 08826,Republic of Korea [8]Department of Biomedical Engineering,Sogang University,Seoul 04107,Republic of Korea

出　　处：《Acta Pharmaceutica Sinica B》2023年第12期4983-4998,共16页药学学报（英文版）

基　　金：supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF);funded by the Ministry of Education,Science,and Technology(NRF-2016R1A6A1A03012845,NRF-2022M3E5F1017553),Republic of Korea;the Ministry of Food and Drug Safety grant(22213MFDS421),Republic of Korea.

摘　　要：Lipid-coated microbubbles are widely used as an ultrasound contrast agent,as well as drug delivery carriers.However,the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system,and the difficulty of surface modification of microbubbles for active targeting.The exosome,a type of extracellular vesicle,has a preferentially targeting ability for its original cell.In this study,exosome-fused microbubbles(Exo-MBs)were developed by embedding the exosome membrane proteins into microbubbles.As a result,the stability of Exo-MBs is improved over the conventional microbubbles.On the same principle that under the exposure of ultrasound,microbubbles are cavitated and self-assembled into nano-sized particles,and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles(Exo-NPs).The Exo-NPs showed favorable targeting properties to their original cells.A photosensitizer,chlorin e6,was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier.Much higher therapeutic efficacy of photodynamic therapy was confirmed,followed by cancer immunotherapy from immunogenic cell death.We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.

关 键 词：EXOSOMES MICROBUBBLES Photodynamic therapy ULTRASOUND SONOPORATION Cancer immunotherapy Drug delivery 

分 类 号：R943[医药卫生—药剂学]