Departamento de Energia, Medio Ambiente y Salud , Instituto de Ciencia de Materiales de Madrid, Consejo Superior de Investigaciones Cientı́ficas , Madrid 28049 , Spain.
Departamento de Biología , Universidad Autónoma de Madrid , Madrid 28049 Spain.
ACS Appl Mater Interfaces. 2020 Jan 29;12(4):4295-4307. doi: 10.1021/acsami.9b20603. Epub 2020 Jan 15.
We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NPs) with negative, positive, and hydrophobic surfaces that were incorporated outside, inside, or between the lipid bilayers, respectively. To characterize how NPs are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NPs are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 °C with high enthalpy 34.8 J/g) avoiding the leakage of the encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100% of cellular uptake was achieved with a high cell survival (above 80%), which is preserved (83%) for doxorubicin-loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 h, leading to a cell survival reduction of 20%. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating to avoid drug degradation. In conclusion, these drug-loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place, efficiently using an external AMF to reduce or even eliminate side effects.
我们开发了一种可重现且简便的一步策略,用于通过薄层蒸发法合成阿霉素负载磁脂体。约 200nm 的脂质体由 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱(DPPC)和氧化铁纳米颗粒(NPs)组成,具有负、正和疏水性表面,分别位于脂质双层的外部、内部或之间。为了表征 NPs 如何掺入脂质体中,使用了先进的冷冻透射电子显微镜(cryoTEM)和原子力显微镜(AFM)技术。观察到只有当 NPs 附着在脂质体外部时,膜的完整性才得以保留(脂质熔融转变移至 38.7°C,焓值为 34.8 J/g),避免了包裹药物的泄漏,同时具有良好的胶体性质和在交变磁场(AMF)下的最佳加热效率。这些磁脂体已在两种癌细胞系 MDA-MB-231 和 HeLa 细胞中进行了测试。首先,通过高细胞存活率(高于 80%)实现了 100%的细胞摄取,对于载有阿霉素的磁脂体则保留了 83%的存活率。然后,我们证明可以通过远程控制使用非侵入性外部 AMF 触发 1 小时来触发药物释放,从而使细胞存活率降低 20%。202 kHz 和 30 mT 的磁场条件似乎足以产生有效的加热以避免药物降解。总之,这些一步制备的载药磁脂体可用于在特定时间和地点按需释放药物,有效地利用外部 AMF 来减少甚至消除副作用。
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