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基于含二硫键的聚(β-氨基酯)和两性离子氟碳表面活性剂的纳米粒子作为用于脑肿瘤治疗的氧化还原响应性药物载体。

Nanoparticles based on disulfide-containing poly(β-amino ester) and zwitterionic fluorocarbon surfactant as a redox-responsive drug carrier for brain tumor treatment.

机构信息

Graduate School of Tianjin Medical University, Tianjin 300070, People's Republic of China.

出版信息

Nanotechnology. 2018 Dec 7;29(49):495101. doi: 10.1088/1361-6528/aae122. Epub 2018 Sep 13.

Abstract

Malignant brain tumors are often characterized by rapid growth, high invasiveness and poor prognosis. Current methods for brain tumor treatment are dramatically limited because of their inability to cross the blood-brain barrier (BBB) and enter the tumor cells. In this study, we prepared redox-responsive nanoparticles based on disulfide-containing poly(β-amino ester) (ssPBAE) and a zwitterionic fluorocarbon surfactant (Intechem-02) that has a carboxybetaine moiety in molecular structure, and preliminarily evaluated their potential as a drug carrier for brain tumor treatment. These nanoparticles, named as ssPBAEI, had a regular spherical shape and a small size below 50 nm with a relative narrow distribution. Doxorubicin (DOX), as a model chemotherapeutic drug, was efficiently encapsulated into ssPBAEI nanoparticles with a loading content of 25.4%. DOX-loaded ssPBAEI nanoparticles (ssPBAEI/DOX) showed significant redox-responsive in vitro release property and successfully carried DOX across a BBB model, monolayer of human brain capillary endothelial hCMEC/D3 cells. In human glioma LN229 cells, ssPBAEI/DOX nanoparticles were efficiently internalized and DOX was successfully released afterwards, thus significantly inhibited cell growth and induced cell apoptosis. In summary, this nanoparticle system based on ssPBAE and Intechem-02 showed a great potential as a drug carrier for brain tumor treatment.

摘要

恶性脑肿瘤的生长迅速、侵袭性强、预后不良。目前的脑肿瘤治疗方法受到极大限制,因为它们无法穿过血脑屏障(BBB)并进入肿瘤细胞。在这项研究中,我们制备了基于含有二硫键的聚(β-氨基酸酯)(ssPBAE)和一种两性离子氟碳表面活性剂(Intechem-02)的氧化还原响应性纳米粒子,Intechem-02 的分子结构中含有羧基甜菜碱部分,并初步评估了它们作为脑肿瘤治疗药物载体的潜力。这些纳米粒子被命名为 ssPBAEI,具有规则的球形形状和小于 50nm 的小尺寸,分布较窄。阿霉素(DOX)作为一种模型化疗药物,被高效地包封到 ssPBAEI 纳米粒子中,载药量为 25.4%。负载 DOX 的 ssPBAEI 纳米粒子(ssPBAEI/DOX)在体外表现出显著的氧化还原响应性释放特性,并成功地穿过了 BBB 模型,即单层人脑微血管内皮细胞 hCMEC/D3。在人神经胶质瘤 LN229 细胞中,ssPBAEI/DOX 纳米粒子被高效内化,随后成功释放 DOX,从而显著抑制细胞生长并诱导细胞凋亡。总之,基于 ssPBAE 和 Intechem-02 的这种纳米粒子系统显示出作为脑肿瘤治疗药物载体的巨大潜力。

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