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    王太兵, 李颖, 贾卓翰, 郭敏, 胥伟军, 钱军民, 锁爱莉. 白蛋白/透明质酸纳米颗粒制备及递送顺铂效果[J]. 功能高分子学报, 2022, 35(1): 61-67. doi: 10.14133/j.cnki.1008-9357.20210318001
    引用本文: 王太兵, 李颖, 贾卓翰, 郭敏, 胥伟军, 钱军民, 锁爱莉. 白蛋白/透明质酸纳米颗粒制备及递送顺铂效果[J]. 功能高分子学报, 2022, 35(1): 61-67. doi: 10.14133/j.cnki.1008-9357.20210318001
    WANG Taibing, LI Ying, JIA Zhuohan, GUO Min, XU Weijun, QIAN Junmin, SUO Aili. Preparation of Albumin/Hyaluronic Acid Composite Nanoparticles for Cisplatin Delivery[J]. Journal of Functional Polymers, 2022, 35(1): 61-67. doi: 10.14133/j.cnki.1008-9357.20210318001
    Citation: WANG Taibing, LI Ying, JIA Zhuohan, GUO Min, XU Weijun, QIAN Junmin, SUO Aili. Preparation of Albumin/Hyaluronic Acid Composite Nanoparticles for Cisplatin Delivery[J]. Journal of Functional Polymers, 2022, 35(1): 61-67. doi: 10.14133/j.cnki.1008-9357.20210318001

    白蛋白/透明质酸纳米颗粒制备及递送顺铂效果

    Preparation of Albumin/Hyaluronic Acid Composite Nanoparticles for Cisplatin Delivery

    • 摘要: 利用白蛋白模板法,以白蛋白、酰肼化透明质酸和醛基化透明质酸为原料,制备出了白蛋白/透明质酸(B-HA)纳米载体,其可通过配位作用装载顺铂(Cis)得到B-HA/Cis纳米药物。利用FT-IR光谱、1H-NMR谱、透射电子显微镜和电感耦合等离子体-质谱(ICP-MS)等手段表征了B-HA纳米载体的化学结构和B-HA/Cis纳米药物的理化性质。结果表明:该纳米载体装载顺铂后为近球形形貌,平均粒径约为150 nm,顺铂载药率可达10.8%;纳米药物具有还原性/酸性双重响应性药物释放行为。体外细胞实验表明,该纳米载体的细胞毒性可忽略,纳米药物对肝癌(HepG2)细胞有靶向作用,杀伤效果与游离态顺铂相当,杀伤癌细胞的机制是诱导凋亡。白蛋白/透明质酸纳米颗粒是综合性能优异的顺铂靶向递送载体,有望在体内呈现提高疗效、降低毒副作用的效果。

       

      Abstract: Cisplatin (Cis) is one of the typical anti-tumor chemotherapeutic drugs, but its clinical application is restrained by severe toxic side effects and multidrug resistance. However, emerging nanotechnologies have great potential in overcoming the above problems. By means of the albumin templating method, an albumin/hyaluronic acid composite nanocarrier was prepared from albumin, hydrazided hyaluronic acid, and aldehyde hyaluronic acid. Cis could be loaded into the nanocarrier through Pt-hydrazide coordination chemistry. Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectrum, transmission electron microscopy, and inductively coupled plasma mass spectrometry were employed to characterize the chemical structure of nanocarrier and the physiochemical properties of nanomedicine. The results showed that the nanomedicine exhibited a subsphaeroidal morphology with an average size of about 150 nm, and the loading content of Cis was as high as 10.8%. Moreover, the nanomedicine displayed a reduction/acid dual-responsive drug release behavior. In vitro cell experiments showed that the cytotoxicity of the nanocarrier was negligible, and the nanomedicine had good targeting ability towards hepatocellular carcinoma (HepG2) cells. Notably, the effect of nanomedicine in killing HepG2 cells was comparable to free cisplatin. Furthermore, it was found that inducing cell apoptosis was still a major mechanism of killing HepG2 cells by nanomedicine. The albumin/hyaluronic acid composite nanoparticle is a promising nanocarrier with excellent comprehensive performances for the targeting delivery of cisplatin with improved therapeutic efficacy and reduced toxic side effects in vivo .

       

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