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Combined Magnetoliposome Formation and Drug Loading in One Step for Efficient Alternating Current-Magnetic Field Remote-Controlled Drug Release.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-01-06 , DOI: 10.1021/acsami.9b20603 Maria Eugenia Fortes Brollo 1 , Ana Domínguez-Bajo 1 , Andrea Tabero 2 , Vicente Domínguez-Arca 3 , Victor Gisbert 1 , Gerardo Prieto 3 , Christer Johansson 4 , Ricardo Garcia 1 , Angeles Villanueva 2, 5 , María Concepción Serrano 1 , María Del Puerto Morales 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-01-06 , DOI: 10.1021/acsami.9b20603 Maria Eugenia Fortes Brollo 1 , Ana Domínguez-Bajo 1 , Andrea Tabero 2 , Vicente Domínguez-Arca 3 , Victor Gisbert 1 , Gerardo Prieto 3 , Christer Johansson 4 , Ricardo Garcia 1 , Angeles Villanueva 2, 5 , María Concepción Serrano 1 , María Del Puerto Morales 1
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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-sn-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.
中文翻译：
磁脂质体的形成与药物加载相结合，一步实现了高效的交流电-磁场遥控药物释放。
我们已经开发出了一种可重现且简便的一步策略，用于通过使用薄层蒸发法合成负载阿霉素的磁脂质体。约200 nm的脂质体由1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）和氧化铁纳米颗粒（NPs）制成，这些纳米颗粒具有在脂质的外部，内部或之间引入的负，正和疏水表面双层。为了表征NP如何掺入脂质体中，已使用了先进的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（脂类熔体转变在高焓34下转变为38.7°C。8 J / g）避免了封装药物的泄漏，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。这些磁脂质体用两种癌细胞系MDA-MB-231和HeLa细胞进行了测试。首先，具有高细胞存活率（超过80％）实现了100％的细胞摄取，对于阿霉素负载的磁脂质体，该比例得以保留（83％）。然后，我们证明可以通过使用无创外部AMF进行1小时的远程控制来触发阿霉素的释放，从而导致细胞存活率降低20％。202 kHz和30 mT的磁场条件似乎足以产生有效的加热，从而避免药物降解。总之，一步制备的这些载药磁脂质体可用于在特定时间和地点按需释放药物，
更新日期：2020-01-16
中文翻译：
磁脂质体的形成与药物加载相结合，一步实现了高效的交流电-磁场遥控药物释放。
我们已经开发出了一种可重现且简便的一步策略，用于通过使用薄层蒸发法合成负载阿霉素的磁脂质体。约200 nm的脂质体由1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）和氧化铁纳米颗粒（NPs）制成，这些纳米颗粒具有在脂质的外部，内部或之间引入的负，正和疏水表面双层。为了表征NP如何掺入脂质体中，已使用了先进的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（脂类熔体转变在高焓34下转变为38.7°C。8 J / g）避免了封装药物的泄漏，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。这些磁脂质体用两种癌细胞系MDA-MB-231和HeLa细胞进行了测试。首先，具有高细胞存活率（超过80％）实现了100％的细胞摄取，对于阿霉素负载的磁脂质体，该比例得以保留（83％）。然后，我们证明可以通过使用无创外部AMF进行1小时的远程控制来触发阿霉素的释放，从而导致细胞存活率降低20％。202 kHz和30 mT的磁场条件似乎足以产生有效的加热，从而避免药物降解。总之，一步制备的这些载药磁脂质体可用于在特定时间和地点按需释放药物，
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