Bognanni Noemi, Scuderi Chiara, Giglio Valentina, Spiteri Fabio, La Piana Luana, Condorelli Daniele, Barresi Vincenza, Vecchio Graziella
Department of Chemical Science, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Via Santa Sofia 89, 95123, Catania, Italy.
ChemMedChem. 2024 Dec 16;19(24):e202400368. doi: 10.1002/cmdc.202400368. Epub 2024 Nov 8.
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.
环糊精二聚体已被研究作为生物分子的潜在纳米胶囊。两个空腔的存在可以提高包合物的稳定性，起到水溶性差的物质的亲水性夹心作用。在此，我们设计了用生物素作为靶向单元功能化的新型β-和γ-环糊精二聚体，并测试了这些新型生物共轭物作为癌细胞中阿霉素递送系统的性能。生物素可以识别由溶质载体家族5成员6（SLC5A6）基因编码的钠依赖性多种维生素转运体（SMVT）受体，并提高药物的摄取。我们评估了人细胞系中SLC5A6转录本的表达，以选择用于体外研究的最佳细胞模型（MCF-7）。此外，在这些细胞系中，我们研究了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，还研究了可能在阿霉素耐药中起作用的ATP结合盒亚家族G成员2转运体（由ABCG2基因编码）的表达。已确定阿霉素与二聚体复合物的抗增殖活性，以研究生物素部分对MCF-7癌细胞细胞毒性的影响。
