de Morais Flávia Amanda Pedroso, Balbinot Rodolfo Bento, Bakoshi Amanda Beatriz Kawano, Lararin-Bidoia Danielle, da Silva Souza Campanholi Katieli, da Silva Ranulfo Combuca, de França Bruna Martins, Gonçalves Renato Sonchini, Ueda-Nakamura Tânia, de Oliveira Silva Sueli, Caetano Wilker, Nakamura Celso Vataru
Technological Innovation Laboratory in Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá, PR, 87020-900, Brazil.
Department of Chemistry, State University of Maringá, Maringá, PR, 87020-900, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):1013-1021. doi: 10.1007/s00210-024-03379-y. Epub 2024 Aug 24.
Modified theranostic liposomes were created by combining phospholipid 1,2-dipalmitoyl-sn-3-glycerol-phosphatidylcholine with two previously modified Pluronic copolymers covalently linked with spermine and folic acid to carry and stabilize the photosensitizer compound hypericin. After physicochemical characterization, the photocytotoxicity was evaluated against different cancer and healthy cells presenting a strong photodynamic effect. The formulation exhibited no photoactivity without illumination and without hypericin. In vivo, pharmacokinetics biodistribution examined the uptake and theranostic potential of this nanoformulation after its intravenous administration in animal models. Fluorescence images revealed the maximum fluorescence between 0.5-4 h post-tail vein injection, making it an appropriate period for photodynamic treatment. The fluorescence of the entire body was monitored for at least 3 days, indicating that the theranostic procedures can be performed within the 0.5-4 h range after administration, after which the intensity decreases, indicating a potent metabolic ability with no significant side effects. The fluorescence images of the main organs consistently showed a signal during the 1st day of its application. After 48 h, only residues of the modified theranostic formulation were detected in the lungs and thyroid. The promising pharmacokinetics observed in our preliminary studies highlight the potential of this system, making it a worthy candidate for further investigation with tumor models.
通过将磷脂1,2 - 二棕榈酰 - sn - 3 - 甘油 - 磷脂酰胆碱与两种先前修饰的、与精胺和叶酸共价连接的普朗尼克共聚物相结合，制备了改性诊疗脂质体，以携带并稳定光敏剂化合物金丝桃素。经过物理化学表征后，评估了其对不同癌细胞和健康细胞的光细胞毒性，结果显示出强烈的光动力效应。该制剂在无光照且无金丝桃素的情况下无光活性。在体内，药代动力学生物分布研究了该纳米制剂在动物模型中静脉注射后的摄取情况和诊疗潜力。荧光图像显示在尾静脉注射后0.5 - 4小时之间荧光最强，这使其成为光动力治疗的适宜时间段。对全身荧光进行了至少3天的监测，表明诊疗程序可在给药后0.5 - 4小时范围内进行，之后强度降低，表明其具有强大的代谢能力且无明显副作用。主要器官的荧光图像在应用后的第1天持续显示有信号。48小时后，仅在肺和甲状腺中检测到改性诊疗制剂的残留物。我们初步研究中观察到的有前景的药代动力学突出了该系统的潜力，使其成为用肿瘤模型进行进一步研究的有价值的候选者。
