title: Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes.
abstract: Brain tumor lacks effective delivery system for treatment. Focused ultrasound (FUS) can reversibly open BBB without impacts on normal tissues. As a potential drug carrier, cationic liposomes (CLs) have the ability to passively accumulate in tumor tissues for their positive charge. In this study, FUS introduced doxorubicin-loaded cationic liposomes (DOX-CLs) were applied to improve the efficiency of glioma-targeted delivery. Doxorubicin-loaded CLs (DOX-CLs) and quantum dot-loaded cationic liposomes (QD-CLs) were prepared using extrusion technology, and their characterizations were evaluated. With the advantage of QDs in tracing images, the glioma-targeted accumulation of FUS + CLs was evaluated by fluorescence imaging and flow cytometer. Cell survival rate, tumor volume, animal survival time, and brain histology in C6 glioma model were investigated to evaluate the glioma-targeted delivery of FUS + DOX-CLs. DOX-CLs and QD-CLs had suitable nanoscale sizes and high entrapment efficiency. The combined strategy of FUS introduced CLs significantly increased the glioma-targeted accumulation for load drugs. FUS + DOX-CLs showed the strongest inhibition on glioma based on glioma cell in vitro and glioma model in vivo experiments. From MRI and histological analysis, FUS + DOX-CLs group strongly suppressed the glioma progression and extended the animal survival time to 81.2 days. Among all the DOX treatment groups, FUS + DOX-CLs group showed the best cell viability and highest level of tumor apoptosis and necrosis. Combining the advantages of BBB reversible opening by FUS and glioma-targeted binding by CLs, ultrasound introduced cationic liposomes could achieve glioma-targeted delivery, which might be developed as a potential strategy for future brain tumor therapy.
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.|The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Mao
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Tian
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Pian-Pian
authors.initials: PP
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.
authors.forename: Zi-Liang
authors.initials: ZL
authors.lastname: Fan
authors.affiliation: The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China. pharmtds@163.com.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China. lctuua@163.com.|The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. lctuua@163.com.
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004337:Drug Carriers / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D047368:Tumor Burden; D018084:Ultrasonography, Interventional / Q000379:methods*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Cationic liposomes; Doxorubicin; Focused ultrasound; Glioma-targeted delivery; Quantum dots