Karaca Nursenem, Ünlüer Özlem Biçen
Graduate School of Health Sciences, Department of Pharmacognosy, Anadolu University, Eskisehir, Turkey.
Department of Chemistry, Faculty of Science, Eskisehir Technical University , Eskisehir, Turkey.
Protein Pept Lett. 2019;26(4):271-280. doi: 10.2174/0929866526666190119121434.
Molecular imaging of cancer cells using effective drug targeting systems are most interested research area in recent years. Albumin protein is a soluble and most abundant protein in circulatory system. It has a ligand-binding function and acts as a transport protein. Researchers are interested in developing albumin based nanostructured specific anti-tumor drugs in cancer therapy. Pancreatic cancer treatment or drug design for targeted pancreatic cancer cell has great importance due to it has a high mortality rate comparing other cancer types.
In this article, our goal is to develop new targeting nanoparticles based on the conjugation of albumin and Hyaluronic Acid (HA) for pancreatic cancer cells.
In this article, we proposed a new technique for conjugation of albumin (BSA) and HA in nano formation. Firstly, cationic BSA is synthesized. Then, BSA-HA conjugation is obtained by interacted cationic BSA with 1000 ppm HA. Secondly, nano BSA-HA particles and nano BSA particles were synthesized according to AmiNoAcid Decorated and Light Underpinning Conjugation Approach (ANADOLUCA) method which provides a special cross-linking strategy for biomolecules using ruthenium-based amino acid monomer haptens. After characterization studies, cytotoxic activity of synthesized nano BSA-HA particles were determined for PANC-1 ATCC CRL146 cells.
According to the data, nano BSA and nano BSA-HA particles synthesized uniquely using special ruthenium-based amino acid decorated cross-linking agent, (MATyr)2-Ru-(MATyr)2.based on ANDOLUCA method. Characterization results showed that there was not any change in protein folding structures during nano formation process. In addition, nano protein particles gained fluorescence feature. When interacting synthesized nano BSA and nano BSA-HA particles with pancreatic cells, it was found that BSA nanoparticles were usually around cells and membranes, but BSA-HA nanoparticles were identified around the cells, in the cytoplasm inside the cell, and next to the cell nucleus. So, nano BSA-HA particles could be used as cancer cell imaging agent for PANC-1 ATCC CRL146 cells.
The satisfactory conclusion of this study is that synthesized nano BSA-HA particles are fundamental materials for targeting pancreatic cancer cells due to HA receptors located on pancreatic cancer cells and imaging agents due to fluorescence feature of the BSA-HA nanoparticles.
近年来,利用有效的药物靶向系统对癌细胞进行分子成像一直是备受关注的研究领域。白蛋白是循环系统中一种可溶且含量最丰富的蛋白质。它具有配体结合功能并充当转运蛋白。研究人员对开发基于白蛋白的纳米结构特异性抗肿瘤药物用于癌症治疗很感兴趣。由于胰腺癌的死亡率相较于其他癌症类型较高,因此胰腺癌的治疗或针对胰腺癌细胞的药物设计具有重要意义。
在本文中,我们的目标是开发基于白蛋白与透明质酸(HA)共轭的新型靶向纳米颗粒用于胰腺癌细胞。
在本文中,我们提出了一种在纳米形成过程中使白蛋白(BSA)与HA共轭的新技术。首先,合成阳离子型BSA。然后,通过使阳离子型BSA与1000 ppm的HA相互作用获得BSA-HA共轭物。其次,根据氨基酸修饰和光支撑共轭方法(ANADOLUCA)合成纳米BSA-HA颗粒和纳米BSA颗粒,该方法使用基于钌的氨基酸单体半抗原为生物分子提供特殊的交联策略。经过表征研究后,测定合成的纳米BSA-HA颗粒对PANC-1 ATCC CRL146细胞的细胞毒性活性。
根据数据,基于ANADOLUCA方法,使用特殊的基于钌的氨基酸修饰交联剂(MATyr)2-Ru-(MATyr)2独特地合成了纳米BSA和纳米BSA-HA颗粒。表征结果表明在纳米形成过程中蛋白质折叠结构没有任何变化。此外,纳米蛋白质颗粒获得了荧光特性。当使合成的纳米BSA和纳米BSA-HA颗粒与胰腺细胞相互作用时,发现BSA纳米颗粒通常围绕细胞和细胞膜,但BSA-HA纳米颗粒在细胞周围、细胞内的细胞质中以及细胞核旁边被识别。因此,纳米BSA-HA颗粒可作为PANC-1 ATCC CRL146细胞的癌细胞成像剂。
本研究令人满意的结论是,合成的纳米BSA-HA颗粒是靶向胰腺癌细胞的基础材料,这是由于胰腺癌细胞上存在HA受体,同时由于BSA-HA纳米颗粒的荧光特性,它也是成像剂。