Nešić Maja D, Dučić Tanja, Liang Xinyue, Algarra Manuel, Mi Lan, Korićanac Lela, Žakula Jelena, Kop Tatjana J, Bjelaković Mira S, Mitrović Aleksandra, Gojgić Cvijović Gordana D, Stepić Milutin, Petković Marijana
Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
ALBA-CELLS Synchrotron, MIRAS Beamline, Cerdanyola del Vallès, Spain.
Int J Biol Macromol. 2020 Dec 15;165(Pt B):2541-2549. doi: 10.1016/j.ijbiomac.2020.10.141. Epub 2020 Oct 23.
Objects of the present study are improved fullerene C drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.
本研究的目的是通过微生物多糖（左聚糖（LEV）、普鲁兰多糖（PUL））及其疏水化胆固醇衍生物（CHL和CHP）对富勒烯C进行包封，以改善其药物载体性能，这些多糖与癌细胞表现出更好的相互作用。测定了颗粒的zeta电位、多分散指数和直径，并测试了它们对三种癌细胞系的细胞毒性。通过同步辐射（SR）傅里叶变换红外光谱显微镜结合主成分分析（PCA）分析了HeLa细胞中的生化变化。在用LEV-C处理的HeLa细胞中发生了最显著的变化，这些变化对应于蛋白质区域的变化，即酰胺I带，脂质体结构的变化和膜流动性的变化也很明显。LEV-C也诱导了最高的细胞毒性。在HeLa细胞中，细胞毒性不能严格地与脂质、蛋白质和核酸的生化变化相关联，但这些发现对研究基于C的纳米颗粒与细胞生物分子的相互作用机制有重要贡献。总之，LEV、PUL、CHL和CHP增强了富勒烯C作为靶向药物递送系统的潜力，能够在HeLa癌细胞中诱导特定的细胞内变化。
