Cyclodextrin Dimers Functionalized with Biotin as Nanocapsules for Active Doxorubicin Delivery Against MCF-7 Breast Cell Line.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL ChemMedChem Pub Date : 2024-09-09 DOI:10.1002/cmdc.202400368

Noemi Bognanni, Chiara Scuderi, Valentina Giglio, Fabio Spiteri, Luana La Piana, Daniele Condorelli, Vincenza Barresi, Graziella Vecchio

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Abstract

Cyclodextrin dimers have been investigated as potential nanocapsules of biomolecules. The presence of two cavities can improve the stability of inclusion complexes, working as a hydrophilic sandwich of poorly water-soluble species. Here, we designed new β- and γ-cyclodextrin dimers functionalized with biotin as a targeting unit and tested the new bioconjugates as doxorubicin delivery systems in cancer cells. Biotin can recognize the Sodium-dependent Multivitamin Transporter (SMVT) receptor, encoded by the Solute Carrier Family 5 Member 6 (SLC5A6) gene and improve the uptake of drugs. We evaluated the expression of the SLC5A6 transcript in human cell lines to select the best cell model (MCF-7) for the in vitro studies. Furthermore, in the cell lines, we investigated the transcript levels of genes correlated to biotin cell availability, Holocarboxylase Synthetase (or HCS encoded by HLCS gene) and Biotinidase (encoded by BTD gene) enzymes. Moreover, the expression of ATP Binding Cassette Subfamily G Member 2 transporter (encoded by ABCG2 gene), which may play a role in doxorubicin resistance, has been investigated. The antiproliferative activity of the doxorubicin complexes with the dimers has been determined to study the effect of the biotin moiety on the cytotoxicity in MCF-7 cancer cells.

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用生物素功能化的环糊精二聚体作为纳米胶囊，可对 MCF-7 乳腺癌细胞株有效释放多柔比星。

环糊精二聚体被研究用作潜在的生物分子纳米胶囊。两个空腔的存在可以提高包合物的稳定性，成为水溶性差的物种的亲水夹层。在这里，我们设计了以生物素为靶向单元的新型β-和γ-环糊精二聚体，并将这种新型生物共轭物作为多柔比星递送系统在癌细胞中进行了测试。生物素可以识别由溶质运载家族 5 号成员 6（SLC5A6）基因编码的钠依赖性多维生素转运体（SMVT）受体，从而提高药物的吸收。我们评估了 SLC5A6 转录本在人类细胞系中的表达情况，选择了最佳细胞模型（MCF-7）进行体外研究。此外，我们还研究了细胞系中与生物素细胞可用性相关的基因、全羧化酶合成酶（或由 HLCS 基因编码的 HCS）和生物素酶（由 BTD 基因编码）的转录水平。此外，还研究了可能在多柔比星耐药性中发挥作用的 ATP 结合盒式 G 亚家族成员 2 转运体（由 ABCG2 基因编码）的表达情况。测定了多柔比星与二聚体复合物的抗增殖活性，以研究生物素分子对 MCF-7 癌细胞细胞毒性的影响。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.