Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
Department of Biosensors, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10 Str., 10-748 Olsztyn, Poland.
Int J Mol Sci. 2021 Jan 29;22(3):1362. doi: 10.3390/ijms22031362.
The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs' side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with = 24, there are two other competing contributions that enable increasing under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. The in vitro cytotoxicity/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cells, and low activity against healthy MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.
化疗药物与纳米笼蛋白脱铁铁蛋白（APO）的相互作用是有效封装和释放基于 APO 的控释药物传递系统中高毒性药物的关键特征。封装可以减轻药物的副作用、对健康细胞的附带损害和不良反应。本文研究了蒽环类药物与 APO 的相互作用，以评估药物脂溶性对其包封过剩和体外活性的影响。研究了具有 0.8 至 15 的脂溶性的蒽环类药物，包括多柔比星（DOX）、表柔比星（EPI）、柔红霉素（DAU）和伊达比星（IDA）。我们发现，除了与 = 24 的氢键超分子聚集体形成外，还有另外两种竞争贡献可以在强极性相互作用下（APO（DOX））或在强疏水性相互作用下（APO（IDA））增加 。使用 UV-Vis、荧光、圆二色性和 FTIR 光谱研究了封装/释放过程。体外细胞毒性/生长抑制试验和流式细胞术证实了 APO（药物）对靶向 MDA-MB-231 腺癌和 HeLa 细胞的高凋亡活性，以及对健康 MCF10A 细胞的低活性，证明了纳米药物的靶向能力。开发了蒽环类药物与 APO 纳米载体之间分子相互作用的模型，并将推导的关系与实验结果进行了比较。
