Institute of Biomedical Optics, University of Lübeck, Peter-Monnik-Weg 4, 23562 Lübeck, Germany.
Por-Lab, Porphyrin-Laboratories GmbH, Blauenkrog 15, 23684 Scharbeutz, Germany.
Mol Pharm. 2020 Aug 3;17(8):2779-2788. doi: 10.1021/acs.molpharmaceut.9b01173. Epub 2020 Jul 13.
The delivery of therapeutic drugs to a specific cellular site is a challenge in the treatment of different diseases. Liposomes have been widely studied as vehicles for drug delivery, and recent research begins to show the potential of the light-controlled opening of liposomes. Liposomes with photoactive molecules can release their cargo upon light irradiation for localized drug release. Light as an external trigger can be controlled temporally and spatially with high precision. In this study, we investigate the potential of light-sensitive liposomes with four photosensitizers and two lipid formulations for light-induced release. To investigate the permeabilization of the liposomes, calcein was encapsulated in high concentration inside the liposomes so that the calcein fluorescence is quenched. If calcein is released from the liposome, quenching is avoided, and the fluorescence increases. We demonstrated that liposomes with the sensitizers benzoporphyrine derivative monoacid (BPD), chlorine e6 (Ce6), Al(III) phthalocyanine chloride disulfonic acid (AlPcS), and 5,10-di-(4-hydroxyphenyl)-15,20-diphenyl-21,23-porphyrin (5,10-DiOH) release cargo effectively after irradiation. Liposomes with 5,10-DiOH showed a quicker release compared to the other sensitizers upon irradiation at 420 nm. Further, we observed through fractionated irradiation, that most of the release took place during light application, while the permeability of the liposome decreased shortly after light exposure. This effect was stronger with liposomes containing less cholesterol.
将治疗药物递送到特定的细胞部位是治疗不同疾病的一个挑战。脂质体作为药物递送的载体已经得到了广泛的研究,最近的研究开始显示出光控脂质体打开的潜力。带有光活性分子的脂质体可以在光照下释放其货物,实现局部药物释放。光作为外部触发可以以高精度进行时间和空间上的控制。在这项研究中,我们研究了四种光敏感分子和两种脂质配方的光敏感脂质体在光诱导释放方面的潜力。为了研究脂质体的通透性,我们将高浓度的钙黄绿素包裹在脂质体内部,使钙黄绿素荧光猝灭。如果钙黄绿素从脂质体中释放出来,猝灭就会避免,荧光就会增强。我们证明了,在光照下,含有敏化剂苯并卟啉衍生物单酸(BPD)、氯 e6(Ce6)、铝(III)酞菁二磺酸钠(AlPcS)和 5,10-二(4-羟基苯基)-15,20-二苯基-21,23-卟啉(5,10-DiOH)的脂质体能够有效地释放货物。与其他敏化剂相比,5,10-DiOH 脂质体在 420nm 光照下释放更快。此外,我们通过分段照射观察到,大部分释放发生在光照过程中,而在光暴露后不久,脂质体的通透性就会降低。这种效应在含有较少胆固醇的脂质体中更为明显。