Nitica Stefan, Fizesan Ionel, Dudric Roxana, Loghin Felicia, Lucaciu Constantin Mihai, Iacovita Cristian
Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, 6 Pasteur St., 400349 Cluj-Napoca, Romania.
Department of Toxicology, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 6A Pasteur St., 400349 Cluj-Napoca, Romania.
Pharmaceutics. 2022 Nov 18;14(11):2501. doi: 10.3390/pharmaceutics14112501.
The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm. Below this threshold, the subsequent exposure to an alternating magnetic field (20-30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX.
由于高温与化疗效果之间的协同作用,磁热疗与化疗相结合被认为是癌症治疗中一种很有前景的策略,这种协同作用可进一步用于靶向和远程控制药物释放。在本文中,我们报告了一种简单、快速且可重复的方法,用于制备负载阿霉素(DOX)的热敏磁脂质体(TsMLs),该方法包括从先前获得的油包水微乳液形成脂质凝胶,该微乳液具有分散在热敏脂质有机溶液(转变温度约为43°C)中的含磁性纳米颗粒(MNPs)的细小水滴,然后用DOX水溶液使凝胶水合。所制备的热敏磁脂质体(TsMLs)直径约为300 nm,DOX包封率为40%。最适合掺入脂质体水腔的MNPs是锌铁氧体,在300 K时具有非常低的矫顽场(7 kA/m),接近超顺磁状态,当分散在水中时最大吸收率(SAR)为1130 W/gFe,当限制在TsMLs内部时为635 W/gFe。在测试浓度范围内孵育48小时后,未观察到锌铁氧体MNPs或TsMLs对A459癌细胞系有毒性。孵育48小时后,TsMLs中DOX的被动释放从62.5 ug/cm的剂量水平开始诱导毒性。低于该阈值,随后在交变磁场(20 - 30 kA/m,355 kHz)中暴露30分钟,由于掺入的DOX释放,显著降低了A459细胞的活力。我们的结果强烈表明,TsMLs代表了一种利用磁场控制释放DOX进行抗癌治疗的可行策略。
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