Nikolaev Boris, Yakovleva Ludmila, Fedorov Viacheslav, Yudintceva Natalia, Tarasova Daria, Perepelitsa Elizaveta, Dmitrieva Anastasia, Sulatsky Maksim, Srinivasan Sivaprakash, Sonawane Shirish H, Srivastava Anusha, Gupta Sharad, Sonawane Avinash, Combs Stephanie E, Shevtsov Maxim
Laboratory of Biomedical Nanotechnologies, Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 Saint Petersburg, Russia.
Personalized Medicine Centre, Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.
Nanomaterials (Basel). 2025 Mar 21;15(7):475. doi: 10.3390/nano15070475.
The colloidal long-storage stability of nanosized drugs is a crucial factor for pharmacology, as they require much time for robust estimation. The application of bioavailable magnetic nanosuspensions in theranostics is limited by incomplete information about their colloidal stability in the internal media of human organisms. A method for the accelerated temperature stress "aging" of magnetic nanosized suspensions is proposed for the rapid assessment and prediction of the colloidal stability over time of nanosized iron oxide suspensions stabilized by albumin HSA. Colloidal stability is assessed using dynamic light scattering (DLS), fluorescence spectroscopy, electrophoresis, and ion monitoring methods during short- and long-term storage. Rapid assessment is achieved by short high-temperature (70 °C) processing of carboxymethyl-dextran-coated nanosol in the presence of albumin. The role of albumin in the sustained stability of superparamagnetic iron oxide particles (SPIONs) was studied under conditions mimicking blood plasma (pH = 7.4) and endolysosomal cell compartments (pH = 5.5). According to the fluorescence quenching and DLS data, colloidal stability is ensured by the formation of an HSA corona on carboxymethyl-dextran-coated SPIONs and their process of clustering. In the presence of albumin, the colloidal stability of nanoparticles is shown to increase from 80 to 121 days at a storage temperature of 8 °C The prognostic shelf life of magnetic nanosol is estimated by calculating the Van't Hoff's relation for the rate of chemical reactions. The validity of using the Van't Hoff's rule is confirmed by the agreement of the calculated activation energy at 8 °C and 70 °C. The developed method of the accelerated aging of nanoparticles can not only be employed for the estimation of the shelf life of magnetic nanoparticles coated with HSA in vitro but also for assessing the stability of SPIONs applied in vivo.
纳米药物的胶体长期储存稳定性是药理学中的一个关键因素，因为对其进行可靠评估需要很长时间。生物可利用磁性纳米悬浮液在治疗诊断学中的应用受到其在人体内部介质中胶体稳定性信息不完整的限制。本文提出了一种用于磁性纳米悬浮液的加速温度应力“老化”方法，用于快速评估和预测由人血清白蛋白（HSA）稳定的纳米氧化铁悬浮液随时间的胶体稳定性。在短期和长期储存过程中，使用动态光散射（DLS）、荧光光谱、电泳和离子监测方法评估胶体稳定性。通过在白蛋白存在下对羧甲基葡聚糖包被的纳米溶胶进行短时间高温（70°C）处理来实现快速评估。在模拟血浆（pH = 7.4）和内溶酶体细胞区室（pH = 5.5）的条件下，研究了白蛋白在超顺磁性氧化铁颗粒（SPIONs）持续稳定性中的作用。根据荧光猝灭和DLS数据，羧甲基葡聚糖包被的SPIONs上形成HSA冠及其聚集过程确保了胶体稳定性。在白蛋白存在下，纳米颗粒在8°C储存温度下的胶体稳定性从80天增加到121天。通过计算化学反应速率的范特霍夫关系来估计磁性纳米溶胶的预测保质期。在8°C和70°C下计算的活化能的一致性证实了使用范特霍夫规则的有效性。所开发的纳米颗粒加速老化方法不仅可用于体外评估HSA包被的磁性纳米颗粒的保质期，还可用于评估体内应用的SPIONs的稳定性。
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