Angiopep-2 conjugated nanoparticles loaded with doxorubicin for the treatment of primary central nervous system lymphoma,Biomaterials Science

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Angiopep-2 conjugated nanoparticles loaded with doxorubicin for the treatment of primary central nervous system lymphoma
Biomaterials Science ( IF 5.8 ) Pub Date : 2019/12/11 , DOI: 10.1039/c9bm01750j
Xiao-Xiao Shi _{1,

2,

3,

4,

5} , Wei-Min Miao _{3,

4,

5,

6,

7} , Di-Wen Pang _{1,

2,

3,

4,

5} , Jia-Si Wu _{3,

4,

5,

7,

8} , Qi-Song Tong _{3,

4,

5,

7,

8} , Jia-Xian Li _{1,

2,

3,

4,

5} , Jia-Qi Luo _{3,

4,

5,

7,

8} , Wen-Yu Li _{4,

5,

9,

10} , Jin-Zhi Du _{1,

2,

3,

4,

5} , Jun Wang _{1,

2,

3,

4,

5}

Affiliation

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood–brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

中文翻译：

载有阿霉素的Angiopep-2共轭纳米颗粒治疗原发性中枢神经系统淋巴瘤

原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见的脑肿瘤。它的治疗功效远低于传统的淋巴瘤，主要是由于存在血脑屏障（BBB），阻碍了药物在疾病部位的有效传递和沉积。Angiopep-2（ANG）可以靶向脑毛细血管内皮细胞（BCEC）表面上的低密度脂蛋白受体相关蛋白（LRP），并具有高BBB转运能力。在这项研究中，我们设计了ANG共轭聚（乙二醇）-b-聚（ε-己内酯）（PEG- b-PCL）（APP）纳米颗粒可递送阿霉素（DOX），用于治疗PCNSL。我们的数据表明，与对照纳米颗粒相比，靶向APP纳米颗粒显示出BCEC明显增加的细胞摄取。在颅内SU-DHL-2-LUC淋巴瘤异种移植小鼠模型中，APP增强了肿瘤组织中的药物沉积，并且载有DOX的APP（APP @ DOX）表现出比游离DOX和非靶向PP @ DOX更好的治疗效果，后者显着延长小鼠的生存时间。

更新日期：2020-03-03

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