Bognanni Noemi, Viale Maurizio, La Piana Luana, Strano Simone, Gangemi Rosaria, Lombardo Cinzia, Cambria Maria Teresa, Vecchio Graziella
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy.
UOC Bioterapie, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, Italy.
Pharmaceutics. 2023 Jan 21;15(2):374. doi: 10.3390/pharmaceutics15020374.
In the last years, nanoparticles based on cyclodextrins have been widely investigated for the delivery of anticancer drugs. In this work, we synthesized nanoparticles with a hyaluronic acid backbone functionalized with cyclodextrins under green conditions. We functionalized hyaluronic acid with two different molecular weights (about 11 kDa and 45 kDa) to compare their behavior as doxorubicin delivery systems. We found that the new hyaluronan-cyclodextrin conjugates increased the water solubility of doxorubicin. Moreover, we tested the antiproliferative activity of doxorubicin in the presence of the new cyclodextrin polymers in SK-N-SH and SK-N-SH-PMA (over-expressing CD44 receptor) cancer cells. We found that hyaluronan-cyclodextrin conjugates improved the uptake and antiproliferative activity of doxorubicin in the SK-N-SH-PMA compared to the SK-N-SH cell line at the ratio 8/1 doxorubicin/polymer. Notably, the system based on hyaluronan (45 kDa) was more effective as a drug carrier and significantly reduced the IC value of doxorubicin by about 56%. We also found that hyaluronic acid polymers determined an improved antiproliferative activity of doxorubicin (IC values are on average reduced by about 70% of free DOXO) in both cell lines at the ratio 16/1 doxorubicin/polymer.
在过去几年中，基于环糊精的纳米颗粒已被广泛研究用于抗癌药物的递送。在这项工作中，我们在绿色条件下合成了具有环糊精功能化透明质酸主链的纳米颗粒。我们用两种不同分子量（约11 kDa和45 kDa）的透明质酸进行功能化，以比较它们作为阿霉素递送系统的行为。我们发现新的透明质酸 - 环糊精共轭物提高了阿霉素的水溶性。此外，我们在SK - N - SH和SK - N - SH - PMA（过表达CD44受体）癌细胞中测试了在新的环糊精聚合物存在下阿霉素的抗增殖活性。我们发现，与SK - N - SH细胞系相比，在阿霉素/聚合物比例为8/1时，透明质酸 - 环糊精共轭物提高了阿霉素在SK - N - SH - PMA中的摄取和抗增殖活性。值得注意的是，基于透明质酸（45 kDa）的系统作为药物载体更有效，并且阿霉素的IC值显著降低了约56%。我们还发现，在阿霉素/聚合物比例为16/1时，透明质酸聚合物在两种细胞系中均提高了阿霉素的抗增殖活性（IC值平均比游离阿霉素降低约70%）。
