Nanohybrid Liposomal Cerasomes with Good Physiological Stability and Rapid Temperature Responsiveness for High Intensity Focused Ultrasound Triggered Local Chemotherapy of Cancer

被引:142
作者
Liang, Xiaolong [1 ]
Gao, Jing [2 ]
Jiang, Lingdong [3 ]
Luo, Jianwen [2 ]
Jing, Lijia [3 ]
Li, Xiaoda [3 ]
Jin, Yushen [3 ]
Dai, Zhifei [1 ]
机构
[1] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China
[2] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100871, Peoples R China
[3] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
cerasomes; triggered drug release; high intensity focused ultrasound; local chemotherapy; thermosensitive liposome; CONTROLLED DRUG-RELEASE; TUMOR XENOGRAFT MODEL; SENSITIVE LIPOSOMES; THERMOSENSITIVE LIPOSOMES; IN-VITRO; MILD HYPERTHERMIA; MACROMOLECULAR THERAPEUTICS; DELIVERY SYSTEMS; SOLID TUMORS; DOXORUBICIN;
D O I
10.1021/nn507482w
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in combination with the component lipids of conventional low temperature sensitive liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm, exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug loaded HTSCs showed much longer blood circulation time (half-life >8.50 +/- 1.49 h) than conventional LTSLs (0.92 +/- 0.17 h). An in vitro study demonstrated that the drug loaded HTSCs are highly stable at 37 degrees C and show a burst release at 42 degrees C, providing a capability to act synergistically against tumors. We found that the HTSCs with a proportion of 43.25% of CFL could release more than 90% hydrophilic drugs in 1 min at an elevated temperature of 42 degrees C generated by HIFU exposure. After intravenous injection of doxorubicin (DOX) loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited. Therefore, the drug loaded HTSCs combined with HIFU hold great potential for efficient local chemotherapy of cancer due to the ability to deliver high concentration of chemotherapy drugs directly to the tumor, achieve maximum therapeutic efficacy and minimal side effects, and avoid the damage to the healthy tissues caused by systemic administration of drugs.
引用
收藏
页码:1280 / 1293
页数:14
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