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鬼臼毒素与纳米系统的生物共轭：提升其生物制药及抗肿瘤特性的方法

Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile.

作者信息

Miranda-Vera Carolina, Hernández Ángela-Patricia, García-García Pilar, Díez David, García Pablo A, Castro María Ángeles

机构信息

Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain.

Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, 37008 Salamanca, Spain.

出版信息

Pharmaceuticals (Basel). 2025 Jan 26;18(2):169. doi: 10.3390/ph18020169.

DOI:10.3390/ph18020169
PMID:40005983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11859694/
Abstract

Podophyllotoxin is a natural compound belonging to the lignan family and is well-known for its great antitumor activity. However, it shows several limitations, such as severe side effects and some pharmacokinetics problems, including low water solubility, which hinders its application as an anticancer agent. Over the past few years, antitumor research has been focused on developing nanotechnology-based medicines or nanomedicines which allow researchers to improve the pharmacokinetic properties of anticancer compounds. Following this trend, podophyllotoxin nanoconjugates have been obtained to overcome its biopharmaceutical drawbacks and to enhance its antitumor properties. The objective of this review is to highlight the advances made over the past few years (2017-2023) regarding the inclusion of podophyllotoxin in different nanosystems. Among the huge variety of nanoconjugates of diverse nature, drug delivery systems bearing podophyllotoxin as cytotoxic payload are organic nanoparticles mainly based on polymer carriers, micelles, and liposomes. Along with the description of their pharmacological properties as antitumorals and the advantages compared to the free drug in terms of biocompatibility, solubility, and selectivity, we also provide insight into the synthetic procedures developed to obtain those podophyllotoxin-nanocarriers. Typical procedures in this regard are self-assembly techniques, nanoprecipitations, or ionic gelation methods among others. This comprehensive perspective aims to enlighten the medicinal chemistry community about the tendencies followed in the design of new podophyllotoxin-based drug delivery systems, their features and applications.

摘要

鬼臼毒素是一种属于木脂素家族的天然化合物，以其强大的抗肿瘤活性而闻名。然而，它存在一些局限性，如严重的副作用和一些药代动力学问题，包括水溶性低，这阻碍了它作为抗癌药物的应用。在过去几年中，抗肿瘤研究一直集中在开发基于纳米技术的药物或纳米药物，这使研究人员能够改善抗癌化合物的药代动力学性质。顺应这一趋势，已获得鬼臼毒素纳米缀合物以克服其生物制药方面的缺点并增强其抗肿瘤特性。本综述的目的是突出过去几年（2017 - 2023年）在将鬼臼毒素纳入不同纳米系统方面取得的进展。在种类繁多、性质各异的纳米缀合物中，以鬼臼毒素作为细胞毒性载荷的药物递送系统主要是基于聚合物载体、胶束和脂质体的有机纳米颗粒。除了描述它们作为抗肿瘤药物的药理性质以及与游离药物相比在生物相容性、溶解性和选择性方面的优势外，我们还深入介绍了为获得这些鬼臼毒素 - 纳米载体而开发的合成方法。这方面的典型方法包括自组装技术、纳米沉淀法或离子凝胶法等。这一全面的视角旨在让药物化学界了解新型基于鬼臼毒素的药物递送系统设计中所遵循的趋势、它们的特点和应用。

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