Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy.
Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy.
复制标题
DOI：
10.1088/0957-4484/22/26/265101
复制
发表时间：
2011-07-01
期刊：
影响因子：
3.5
通讯作者：
Sengupta S
中科院分区：
文献类型：
--
作者：
Paraskar A;Soni S;Basu S;Amarasiriwardena CJ;Lupoli N;Srivats S;Roy RS;Sengupta S
顺铂作为大多数癌症的一线化疗药物，由于肾毒性而受到剂量限制。虽然这种毒性可以通过纳米技术解决，但之前设计顺铂纳米颗粒的尝试受到了对顺铂效力影响的限制。在这里，我们报告了一种新的顺铂纳米粒子的合理工程利用一种新的聚乙二醇官能化的聚异丁烯-马来酸（PEG-PIMA）的共聚物，它可以配合顺铂（II）通过一个monocarboxylato和配位键。我们表明，这种复合物自组装成纳米颗粒，并表现出与游离顺铂（IC 50 = 0.44 ± 0.09 μM）相当的IC 50 = 0.77 ± 0.11μM。纳米颗粒被内化到癌细胞的内溶酶体区室中，并以pH依赖性方式释放顺铂。此外，纳米颗粒在体内4 T1乳腺癌模型中表现出显著改善的抗肿瘤功效，具有有限的肾毒性，这可以通过在肿瘤中具有降低的肾浓度的优先生物分布来解释。我们的研究结果表明，PEG-PIMA-顺铂纳米颗粒可以成为一个有吸引力的解决方案，顺铂化疗的挑战。
The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While, this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) co-polymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibit an IC50 = 0.77 ± 0.11μM comparable to that of free cisplatin (IC50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and releases cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibited significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.
登录
查看更多内容
DOI：
10.1073/pnas.1007026107
发表时间：
2010-07-13
影响因子：
11.1
作者：
Paraskar, Abhimanyu S.;Soni, Shivani;Sengupta, Shiladitya
通讯作者：
Sengupta, Shiladitya
影响因子：
10.8
作者：
Fujiyama, J;Nakase, Y;Hagiwara, A
通讯作者：
Hagiwara, A
影响因子：
15.9
作者：
Leong, Chee-Onn;Vidnovic, Nick;Ellisen, Leif W.
通讯作者：
Ellisen, Leif W.
影响因子：
8.8
作者：
White, S. C.;Lorigan, P.;Margison, G. P.;Margison, J. M.;Martin, F.;Thatcher, N.;Anderson, H.;Ranson, M.
通讯作者：
Ranson, M.
影响因子：
46.9
作者：
Choi, Hak Soo;Liu, Wenhao;Frangioni, John V.
通讯作者：
Frangioni, John V.