凝集素门控和聚糖官能化的介孔二氧化硅纳米容器，用于靶向过度表达Lewis X抗原的癌细胞<a href="#fn1" title="可用的电子补充信息（ESI）：合成后的MSN和提取的MSN的PXRD模式； MSN和固体S3的TEM图像； N2吸附-解吸等温线用于MSN和孔径分布；以及ATTO 430LS染料在细胞培养基中从固体S3的释放曲线。参见DOI：10.1039 / c7nr06415b">†</a>,Nanoscale

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凝集素门控和聚糖官能化的介孔二氧化硅纳米容器，用于靶向过度表达Lewis X抗原的癌细胞 †
Nanoscale ( IF 5.8 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1039/c7nr06415b
R. Bhat _{1,

2,

3,

4,

5} , I. García _{5,

6,

7,

8,

9} , E. Aznar _{1,

2,

3,

4,

5} , B. Arnaiz _{5,

6,

7,

8,

9} , M. C. Martínez-Bisbal _{1,

2,

3,

4,

5} , L. M. Liz-Marzán _{5,

6,

7,

8,

9} , S. Penadés _{5,

6,

7,

8,

9} , R. Martínez-Máñez _{1,

2,

3,

4,

5}

Affiliation

门控介孔二氧化硅纳米颗粒可以通过施加预定的刺激来输送有效载荷，因此是很有前途的药物输送系统。尽管它们起着重要的作用，但相对较少的重点放在主动靶向碳水化合物肿瘤细胞膜受体的门控系统的设计上。我们在本文中描述了一种新的Lewis X（Le ^x）抗原靶向的递送系统，该系统包括负载有ATTO 430LS染料，以Le ^x衍生物（1）功能化并以岩藻糖特异性碳水化合物结合蛋白（Aleuria aurantia lectin（AAL））。该设计利用了AAL对Le ^x的亲和力在某些癌细胞中过表达的受体。在细胞附近，AAL从MSN分离以结合Le ^x，并且细胞中的选择素在门控MSN中结合Le ^x，从而诱导货物递送。门控MSN对结肠癌DLD-1细胞无毒，传递的ATTO 430LS染料与DLD-1细胞表面过表达的Le ^x抗原量相关。这是使用生物学相关的聚糖进行封端（通过与AAL相互作用）和靶向（通过与在细胞膜上过度表达的Le ^x相互作用）的MSN的少数几个例子之一。

"点击查看英文标题和摘要"

Lectin-gated and glycan functionalized mesoporous silica nanocontainers for targeting cancer cells overexpressing Lewis X antigen†

Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Le^x) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Le^x derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Le^x overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Le^x, and selectins in the cells bind Le^x in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Le^x antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Le^x at the cell membrane).

更新日期：2017-11-22

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