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负载顺铂的甲氧基聚(乙二醇)-嵌段-聚(L-谷氨酸-co-L-苯丙氨酸)纳米颗粒对人乳腺癌细胞的作用

Cisplatin loaded methoxy poly (ethylene glycol)-block-Poly (L-glutamic acid-co-L-Phenylalanine) nanoparticles against human breast cancer cell.

作者信息

Ahmad Zaheer, Tang Zhaohui, Shah Afzal, Lv Shixian, Zhang Dawei, Zhang Ying, Chen Xuesi

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China; Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.

出版信息

Macromol Biosci. 2014 Sep;14(9):1337-45. doi: 10.1002/mabi.201400109. Epub 2014 Jun 16.

Abstract

Cisplatin (cis-diaminodichloroplatinum, CDDP) loaded methoxy poly (ethylene glycol)-block-poly (glutamic acid-co-phenyl alanine) [mPEG-b-P (Glu10 -co-Phe10 ) (PGlu10 ) and mPEG-b-P (Glu20 -co-Phe10 ) (PGlu20 )] nanoparticles with two different formulations (CDDP/PGlu10 and CDDP/PGlu20 ) are successfully developed in uniformly sizes. In 190 h, the CDDP/PGlu10 shows 30% release at physiological pH and 39% at lysosomal pH. Similarly, the CDDP/PGlu20 shows 60% release at physiological pH and 90% release at lysosomal pH. The sustained and controlled release of both formulations evidences the in vitro longevity of the nanoparticles. The cell proliferation inhibition of nanoparticles against human breast cancer cell line ZR-75-30 is dose and time dependent. Both CDDP/PGlu10 and CDDP/PGlu20 show excellent hemo compatibility as evaluated by hemolysis experiments. The in vivo fate of CDDP and CDDP loaded nanoparticles are evaluated by pharmacokinetics studies. Free CDDP underwgoes instant platinum concentration decrease after intravenous administration with 1.0 wt% left in 24 h while the CDDP loaded nanoparticles show prolonged blood circulation time with 5 wt% (CDDP/PGlu20 ) to 14 wt% (CDDP/PGlu10 ) left in 24 h. This prolonged blood circulation of CDDP loaded nanoparticles makes them as promising nanocarriers for tumor targeting delivery.

摘要

成功制备了两种不同配方(顺铂/聚谷氨酸10(CDDP/PGlu10)和顺铂/聚谷氨酸20(CDDP/PGlu20))的负载顺铂(顺二氨基二氯铂,CDDP)的甲氧基聚(乙二醇)-嵌段-聚(谷氨酸-共-苯丙氨酸)[甲氧基聚乙二醇-b-聚(谷氨酸10-共-苯丙氨酸10)(PGlu10)和甲氧基聚乙二醇-b-聚(谷氨酸20-共-苯丙氨酸10)(PGlu20)]纳米颗粒,其尺寸均匀。在190小时内,CDDP/PGlu10在生理pH值下释放30%,在溶酶体pH值下释放39%。同样,CDDP/PGlu20在生理pH值下释放60%,在溶酶体pH值下释放90%。两种配方的持续控释证明了纳米颗粒在体外的长效性。纳米颗粒对人乳腺癌细胞系ZR-75-30的细胞增殖抑制作用具有剂量和时间依赖性。通过溶血实验评估,CDDP/PGlu10和CDDP/PGlu20均表现出优异的血液相容性。通过药代动力学研究评估了顺铂和负载顺铂的纳米颗粒的体内命运。静脉注射后,游离顺铂的铂浓度立即降低,24小时后剩余1.0 wt%,而负载顺铂的纳米颗粒显示出血液循环时间延长,24小时后剩余5 wt%(CDDP/PGlu20)至14 wt%(CDDP/PGlu10)。负载顺铂的纳米颗粒的这种延长的血液循环使其成为用于肿瘤靶向递送的有前景的纳米载体。

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