Fus-Kujawa Agnieszka, Sieroń Łukasz, Dobrzyńska Estera, Chajec Łukasz, Mendrek Barbara, Jarosz Natalia, Głowacki Łukasz, Dubaj Kamila, Dubaj Wojciech, Kowalczuk Agnieszka, Bajdak-Rusinek Karolina
Department of Medical Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Medykow 18 Street, 40-752 Katowice, Poland.
Animal Histology and Embryology Group, Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia in Katowice, 40-007 Katowice, Poland.
Biomolecules. 2022 Apr 19;12(5):608. doi: 10.3390/biom12050608.
Apoptosis is a widely controlled, programmed cell death, defects in which are the source of various diseases such as neurodegenerative diseases as well as cancer. The use of apoptosis in the therapy of various human diseases is of increasing interest, and the analysis of the factors involved in its regulation is valuable in designing specific carriers capable of targeting cell death. Highly efficient and precisely controlled delivery of genetic material by low-toxic carriers is one of the most important challenges of apoptosis-based gene therapy. In this work, we investigate the effect of the star polymer with 28 poly('-dimethylaminoethyl methacrylate) arms (STAR) on human cells, according to its concentration and structure. We show that star polymer cytotoxicity increases within its concentration and time of cells treatment. Except for cytotoxic effect, we observe morphological changes such as a shrinkage, loss of shape and begin to detach. We also prove DNA condensation after star polymer treatment, one of the most characteristic feature of apoptosis. The results indicate that the use of STAR triggers apoptosis in cancer cells compared to various normal cells, what makes these nanoparticles a promising drug in therapeutic strategy, which targets apoptosis. We demonstrate highlighting potential of star polymers as an innovative tool for anti-cancer therapy.
细胞凋亡是一种广泛受调控的程序性细胞死亡，其缺陷是神经退行性疾病和癌症等各种疾病的根源。利用细胞凋亡治疗各种人类疾病越来越受到关注，分析其调控相关因素对于设计能够靶向细胞死亡的特异性载体具有重要价值。通过低毒载体高效且精确地递送遗传物质是基于细胞凋亡的基因治疗最重要的挑战之一。在这项工作中，我们根据具有28个聚（甲基丙烯酸二甲氨基乙酯）臂的星形聚合物（STAR）的浓度和结构，研究其对人类细胞的影响。我们发现，星形聚合物的细胞毒性在其处理细胞的浓度和时间范围内会增加。除了细胞毒性作用外，我们还观察到形态学变化，如细胞收缩、形状丧失并开始脱离。我们还证明了星形聚合物处理后DNA凝聚，这是细胞凋亡最典型的特征之一。结果表明，与各种正常细胞相比，使用STAR可在癌细胞中引发细胞凋亡，这使得这些纳米颗粒成为靶向细胞凋亡治疗策略中有前景的药物。我们展示了星形聚合物作为抗癌治疗创新工具的突出潜力。
