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凝集素-碳水化合物相互作用:对新型抗癌药物开发的启示

Lectin-Carbohydrate Interactions: Implications for the Development of New Anticancer Agents.

作者信息

de Oliveira Figueiroa Evellyne, Albuquerque da Cunha Cassia Regina, Albuquerque Priscilla B S, de Paula Raiana Apolinario, Aranda-Souza Mary Angela, Alves Matheus Silva, Zagmignan Adrielle, Carneiro-da-Cunha Maria G, Nascimento da Silva Luis Claudio, Dos Santos Correia Maria Tereza

机构信息

Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Pernambuco, CEP 50670-420, Recife, PE, Brazil.

Pos-graduacao em Biologia Parasitaria, Universidade Ceuma, CEP 65075-120, Sao Luis, MA, Brazil.

出版信息

Curr Med Chem. 2017 Nov 17;24(34):3667-3680. doi: 10.2174/0929867324666170523110400.

Abstract

Lectins are a large group of proteins found in animals, plants, fungi, and bacteria that recognize specific carbohydrate targets and play an important role in cell recognition and communication, host-pathogen interactions, embryogenesis, and tissue development. Recently, lectins have emerged as important biomedical tools that have been used in the development of immunomodulatory, antipathogenic, and anticancer agents. Several lectins have been shown to have the ability to discriminate between normal cells and tumor cells as a result of their different glycosylation patterns. Furthermore, the specific binding of lectins to cancer cells has been shown to trigger mechanisms that can promote the death of these abnormal cells. Here, we review the importance of lectins-carbohydrates interactions in cancer therapy and diagnosis. We examine the use of lectins in the modification of nanoparticles (liposomes, solid lipid nanoparticles and other polymers) for anticancer drug delivery. The development of drug delivery systems (liposomes, alginate/chitosan microcapsules, alginate beads) carrying some antitumor lectins is also discussed. In these cases, the processes of cell death induced by these antitumor lectins were also showed (if available). In both cases (lectin-conjugated polymers or encapsulated lectins), these new pharmaceutical preparations showed improved intracellular delivery, bioavailability and targetability leading to enhanced therapeutic index and significantly less side effects.

摘要

凝集素是一类存在于动物、植物、真菌和细菌中的蛋白质,它们能够识别特定的碳水化合物靶点,并在细胞识别与通讯、宿主-病原体相互作用、胚胎发育和组织发育中发挥重要作用。最近,凝集素已成为重要的生物医学工具,被用于免疫调节、抗病原体和抗癌药物的开发。由于正常细胞和肿瘤细胞的糖基化模式不同,几种凝集素已被证明有能力区分它们。此外,凝集素与癌细胞的特异性结合已被证明能触发促进这些异常细胞死亡的机制。在此,我们综述凝集素-碳水化合物相互作用在癌症治疗和诊断中的重要性。我们研究了凝集素在修饰纳米颗粒(脂质体、固体脂质纳米粒和其他聚合物)用于抗癌药物递送方面的应用。还讨论了携带某些抗肿瘤凝集素的药物递送系统(脂质体、海藻酸盐/壳聚糖微胶囊、海藻酸盐珠)的开发。在这些情况下,也展示了这些抗肿瘤凝集素诱导细胞死亡的过程(如果有相关信息)。在这两种情况(凝集素偶联聚合物或包封凝集素)下,这些新型药物制剂均显示出改善的细胞内递送、生物利用度和靶向性,从而提高了治疗指数并显著减少了副作用。

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