Receptor-Mediated Enhanced Cellular Delivery of Nanoparticles Using Recombinant Receptor-Binding Domain of Diphtheria Toxin,Molecular Pharmaceutics

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Receptor-Mediated Enhanced Cellular Delivery of Nanoparticles Using Recombinant Receptor-Binding Domain of Diphtheria Toxin
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2016-12-13 00:00:00 , DOI: 10.1021/acs.molpharmaceut.6b00480
Mahesh Agarwal ₁ , Amaresh Kumar Sahoo ₂ , Biplab Bose _{1,

2}

Affiliation

Antibodies and peptides are often used to home nanoparticles (NPs) to specific cells. Here in this work, we have used recombinant receptor-binding domain of diphtheria toxin (RDT) as a homing molecule for NPs. Diphtheria toxin binds to heparin binding EGF-like growth factor (HB-EGF) through its receptor-binding domain. HB-EGF is often overexpressed as cell surface molecule in various types of cancer. We have prepared monodispersed, spherical PLGA NPs and coated these NPs with RDT. These NPs are characterized by FESEM and FT-IR spectroscopy. Using flow cytometry and fluorescence spectroscopy, we show that coating with RDT increases cellular uptake of PLGA NPs. We further show that RDT-coated nanoparticles are internalized through clathrin-dependent receptor-mediated endocytosis that can be reduced by specific inhibitor. These RDT-coated nanoparticles (RDT-NP) were further used for preferential delivery of Irinotecan, a chemotherapeutic agent, to cells overexpressing HB-EGF. We show that receptor-mediated enhanced uptake of RDT-NPs increases the potency of irinotecan in these cells.

中文翻译：

白喉毒素的重组受体结合域介导的纳米颗粒的受体介导的增强细胞递送。

抗体和肽常用于将纳米颗粒（NP）归巢至特定细胞。在本文中，我们使用了白喉毒素的重组受体结合结构域（RDT）作为NP的归巢分子。白喉毒素通过其受体结合域与肝素结合型EGF样生长因子（HB-EGF）结合。HB-EGF通常在各种类型的癌症中作为细胞表面分子过度表达。我们已经制备了单分散球形PLGA NP，并用RDT涂覆了这些NP。这些NP通过FESEM和FT-IR光谱进行表征。使用流式细胞仪和荧光光谱，我们表明用RDT涂层增加PLGA NPs的细胞摄取。我们进一步表明，RDT包被的纳米粒子通过网格蛋白依赖性受体介导的内吞作用而被内在化，而内吞作用可以被特异性抑制剂所减少。这些带有RDT涂层的纳米颗粒（RDT-NP）进一步用于将伊立替康（一种化学治疗剂）优先递送至过表达HB-EGF的细胞。我们表明，受体介导的RDT-NPs摄取增强会增加伊立替康在这些细胞中的效力。

更新日期：2016-12-13

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