Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 77, Issue 2, Pages 269-280Publisher
SPRINGER
DOI: 10.1007/s00280-015-2926-1
Keywords
Cationic liposomes; Focused ultrasound; Quantum dots; Doxorubicin; Glioma-targeted delivery
Categories
Funding
- National Natural Science Foundation of China [81360195, 81301982, 81571392, 81272160]
- Zhejiang Provincial Natural Science Foundation of China [LY12H31003]
- Zhejiang Provincial Foundation for Health Department [2015ZDA023]
- Wenzhou Bureau of Science and Technology [Y2014730, Y20140726]
- Major Scientific Project of Guangdong Province [2012A080201010]
- Science and Technology Program of Guangzhou, China [201508020001]
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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.
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