Albumin as a “Trojan Horse” for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting†,Biomaterials Science

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Albumin as a “Trojan Horse” for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1039/c8bm00149a
Qian Yin _{1,

2,

3,

4} , Li Tang _{1,

2,

3,

4} , Kaimin Cai _{1,

2,

3,

4} , Xujuan Yang _{2,

3,

4,

5} , Lichen Yin _{1,

2,

3,

4,

6} , Yanfeng Zhang _{1,

2,

3,

4} , Lawrence W. Dobrucki _{2,

3,

4,

7} , William G. Helferich _{2,

3,

4,

5} , Timothy M. Fan _{2,

3,

4,

8} , Jianjun Cheng _{1,

2,

3,

4,

7}

Affiliation

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin. The administration of Alb-NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor vascular permeability resulted in markedly increased tumor accumulation and anti-tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG-NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to improve the cancer targeting efficiency and therapeutic effectiveness of polymeric nanomedicine.

中文翻译：

白蛋白可作为“特洛伊木马”，用于跨肿瘤血管的聚合物纳米复合物跨内皮运输，从而改善癌症靶向性†

尽管聚合纳米共轭物（NCs）在治疗癌症患者方面具有广阔的前景，但由于缺乏将治疗剂有效递送至目标肿瘤部位的作用，其临床应用受到了阻碍。在这里，我们描述了一种白蛋白功能化的聚合物NC（Alb-NC），能够通过小孔介导的胞吞途径穿越内皮屏障，从而更好地靶向癌症。Alb-NC是通过纳米沉淀聚（苯基O）的阿霉素（Doxo）共轭物制备的-羧基酐）带有芳香白蛋白结合结构域，随后进行白蛋白的表面修饰。与携带传统的PEG化NCs（PEG-NCs）相比，将Alb-NCs注入具有有限的肿瘤血管通透性的MCF-7人乳腺癌异种移植物的小鼠体内，可显着增加肿瘤的蓄积和抗肿瘤功效。Alb-NC提供了一种简单，低成本且广泛适用的策略，以提高聚合物纳米药物的靶向癌症效率和治疗效果。

更新日期：2018-03-05

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