Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
ACS Nano. 2015 Feb 24;9(2):1280-93. doi: 10.1021/nn507482w. Epub 2015 Jan 22.
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 °C and show a burst release at 42 °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 °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.
高强度聚焦超声（HIFU）和热敏质体（HTSCs）通过采用质体形成脂质（CFL）与传统低温敏感脂质体（LTSLs）的组成脂质相结合成功组装，包括 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC），1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]（DSPE-PEG-2000）和 1-硬脂酰基-2-羟基-sn-甘油-3-磷酸胆碱（MSPC）。HTSCs 呈球形，平均直径约为 200nm，具有良好的生物相容性。亲水性和疏水性药物都可以有效地封装到 HTSCs 中。此外，通过改变 CFL 与 DPPC 的摩尔比，可以方便地调节 HTSCs 的释放率。载药 HTSCs 的血液循环时间（半衰期>8.50±1.49h）明显长于传统 LTSLs（0.92±0.17h）。体外研究表明，载药 HTSCs 在 37°C 下非常稳定，在 42°C 下会发生爆发式释放，提供了协同对抗肿瘤的能力。我们发现，在 42°C 的高温下，当 CFL 的比例为 43.25%时，HTSCs 可以在 1 分钟内释放超过 90%的亲水性药物。静脉注射 5mg DOX/kg 载阿霉素（DOX）的 HTSCs 后，再进行双重 HIFU 超声处理，可显著抑制荷瘤（MDA-MB-231）腺癌小鼠的肿瘤生长。因此，载药 HTSCs 与 HIFU 联合应用具有很大的潜力，可用于癌症的高效局部化疗，因为它能够将高浓度的化疗药物直接递送到肿瘤部位，达到最大的治疗效果和最小的副作用，并避免药物全身给药对健康组织造成的损害。
