Synthesis of albumin nanoparticles in a water-miscible ionic liquid system, and their applications for chlorambucil delivery to cancer cells
Synthesis of albumin nanoparticles in a water-miscible ionic liquid system, and their applications for chlorambucil delivery to cancer cells
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DOI：
10.1016/j.molliq.2022.120575
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发表时间：
2022-10-18
影响因子：
6
通讯作者：
Cakan-Akdogan, Gulcin
中科院分区：
文献类型：
--
作者：
Akdogan, Yasar;Sozer, Sumeyra Cigdem;Cakan-Akdogan, Gulcin
血清白蛋白是产生用于药物递送应用的生物可降解且无毒的纳米颗粒（NP）的优选蛋白质。不同的方法用于制备血清白蛋白纳米粒大多使用有机溶剂。在这里，我们在离子液体（IL）系统中制备血清白蛋白纳米颗粒。离子液体被认为是绿色和设计溶剂，具有独特的性质，可以取代有机溶剂合成白蛋白纳米颗粒。以水/ TritonTMX（TX-100）、1-丁醇/1-丁基-3-甲基咪唑三氟甲磺酸盐（BmimCF 3SO 3）为微乳体系，采用高速均质器和交联剂戊二醛将牛血清白蛋白（BSA）水溶液转化为BSA纳米粒。所获得的BSA纳米颗粒已被用于药物负载和释放研究与疏水性抗癌药物苯丁酸氮芥（Chl）。载药量随着Chl与BSA NPs孵育的比率的增加而增加。通过紫外-可见光谱法监测药物释放揭示了在前4小时的突释，但三分之二的药物在扩散法后与NP保持在一起。另一方面，Chl负载的BSA NPs的细胞摄取引起显著的MCF 7乳腺癌细胞死亡，而游离Chl和未负载的BSA NPs对细胞活力没有显著影响。此外，在斑马鱼动物模型中进行在IL系统中获得的BSA NP的体内毒性评估。结果表明，斑马鱼体内能够清除BSA纳米颗粒，且没有任何毒副作用，将Chl封装到纳米颗粒中降低了游离Chl的毒性。综上所述，我们发现在BmimCF 3SO 3介导的系统中可以制备尺寸小于200 nm的BSA NPs。它们可用于Chl负载（高达6.9wt%）并持续释放，并且它们在Chl敏感性癌细胞中诱导显著的细胞死亡，在24小时内高达45%。这些结果表明，BSA纳米粒可以交替地在IL系统中制备，并用于药物递送研究。(c)2022爱思唯尔有限公司版权所有。
Serum albumin has been a preferred protein to generate biodegradable and non-toxic nanoparticles (NPs) for drug delivery applications. Different methods applied for the preparation of serum albumin NPs mostly used organic solvents. Here, we prepared serum albumin NPs in an ionic liquid (IL) system. ILs are considered to be green and designer solvents with unique properties that can replace organic solvents in the synthesis of albumin NPs. Bovine serum albumin (BSA) proteins dissolved in water were trans-formed into BSA NPs in a water/ TritonTMX (TX-100), 1-butanol/1-butyl-3-methylimidazolium trifluo-romethanesulfonate (BmimCF3SO3) microemulsion-like system by using a high-speed homogenizer and crosslinker glutaraldehyde. The obtained BSA NPs have been used in drug loading and release studies with a hydrophobic anticancer drug chlorambucil (Chl). Drug loading increased as increasing the ratio of Chl incubated with BSA NPs. Monitoring the drug release by UV-Vis spectroscopy revealed a burst release at first 4 h, but two-thirds of drugs stayed with NPs upon diffusion method. On the other hand, cellular uptake of Chl loaded BSA NPs caused a significant MCF7 breast cancer cell death, whereas free Chl and unloaded BSA NPs did not have a significant effect on the cell viability. Furthermore, in vivo toxicity assessment of BSA NPs obtained in the IL system was conducted in the zebrafish animal model. It showed that zebrafish body is able to eliminate BSA NPs without any toxic side effects and encapsulation of Chl into NPs reduced the toxicity of free Chl. In summary, we showed that BSA NPs with size smaller than 200 nm could be prepared in BmimCF3SO3 mediated system. They can be used for Chl loading (up to 6.9 wt%) with a sustainable release and they induce significant cell death in Chl sensitive cancer cells up to 45% in 24 h. These results indicate that BSA NPs could be prepared alternatively in IL systems and used in drug delivery studies.(c) 2022 Elsevier B.V. All rights reserved.