Demina Polina A, Saveleva Mariia S, Anisimov Roman A, Prikhozhdenko Ekaterina S, Voronin Denis V, Abalymov Anatolii A, Cherednichenko Kirill A, Timaeva Olesya I, Lomova Maria V
Science Medical Centre, Saratov State University, Astrakhanskaya St. 83, 410012 Saratov, Russia.
Department of Physical and Colloid Chemistry, National University of Oil and Gas «Gubkin University», Leninsky Prospekt 65, 119991 Moscow, Russia.
Biomimetics (Basel). 2022 May 12;7(2):61. doi: 10.3390/biomimetics7020061.
Hybrid carriers with the mineral CaCO/FeO core and the protein-tannin shell are attractive for drug delivery applications due to reliable coupling of anticancer drugs with protein-tannin complex and the possibility of remote control over drug localization and delivery by the external magnetic field. This study aims to elucidate the mechanisms of drug release via enzymatic degradation of a protein-tannin carrier shell triggered by proteolytic hydrolases trypsin and pepsin under physiological conditions. To do this, the carriers were incubated with the enzyme solutions in special buffers to maintain the enzyme activity. The time-lapse spectrophotometric and electron microscopy measurements were carried out to evaluate the degradation of the carriers. It was established that the protein-tannin complex demonstrates the different degradation behavior depending on the enzyme type and buffer medium. The incubation in trypsin solution mostly resulted in the protein shell degradation. The incubation in pepsin solution did not affect the protein component; however, the citric buffer stimulates the degradation of the mineral core. The presented results allow for predicting the degradation pathways of the carriers including the release profile of the loaded cargo under physiological conditions. The viability of 4T1 breast cancer cells with mineral magnetic carriers with protein-tannin shells was investigated, and their movement in the fields of action of the permanent magnet was shown.
具有碳酸钙/氧化亚铁矿物核心和蛋白质-单宁外壳的混合载体对于药物递送应用具有吸引力，这是因为抗癌药物与蛋白质-单宁复合物的可靠偶联以及通过外部磁场对药物定位和递送进行远程控制的可能性。本研究旨在阐明在生理条件下，由蛋白水解酶胰蛋白酶和胃蛋白酶引发的蛋白质-单宁载体外壳酶促降解导致药物释放的机制。为此，将载体与酶溶液在特殊缓冲液中孵育以维持酶活性。进行了延时分光光度法和电子显微镜测量以评估载体的降解情况。已确定蛋白质-单宁复合物根据酶类型和缓冲介质表现出不同的降解行为。在胰蛋白酶溶液中孵育主要导致蛋白质外壳降解。在胃蛋白酶溶液中孵育不影响蛋白质成分；然而，柠檬酸缓冲液会刺激矿物核心的降解。所呈现的结果有助于预测载体的降解途径，包括在生理条件下负载货物的释放曲线。研究了具有蛋白质-单宁外壳的矿物磁性载体对4T1乳腺癌细胞的活力，并展示了它们在永磁体作用场中的移动情况。
