Goszczyński Tomasz, Nevozhay Dmitry, Wietrzyk Joanna, Omar Mohamed Salah, Boratyński Janusz
"Neolek" Laboratory of Biomedical Chemistry, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, PAS, Rudolf Weigl 12, Wrocław 53-114, Poland.
Biochim Biophys Acta. 2013 Mar;1830(3):2526-30. doi: 10.1016/j.bbagen.2012.11.005.
The search for new, innovative methods to treat all types of diseases, especially cancer-related ones, is a challenge taken by pharmaceutical companies and academic institutions. The use of conjugates containing widely-known and widely-used bioactive substances is one of the ways to solve this problem. Research into drug binding with macromolecular carrier systems has joined the search for new therapeutic strategies.
The main goal of this paper is the potential offered by the use of fibrinogen derivatives as an antileukemic drug carrier. Physicochemical properties of the obtained conjugate were analyzed, characterizing alterations in relation to the starting carrier and analyzing biological implications. The intraperitoneally (i.p.) inoculated P388 mouse leukemia model for in vivo studies was used.
Conjugates consisting of a fibrinogen derivative with a covalently bound anticancer drug were developed. Carrier preparation and a conjugate synthesis in aqueous solution were formulated, as well as purification of the conjugate was performed. The study showed that the survival of leukemia mice treated with FH-MTX conjugate was indeed significantly longer than survival in both untreated animals (control) and mice treated with unbound MTX. A significant increase in the antileukemic activity of MTX conjugated with hydrolysed fibrinogen was observed as compared with the unconjugated drug. Reported data suggest that hydrolysed fibrinogen can serve as a carrier molecule for the MTX drug with the aim of enhancing its antileukemic activity.
Conjugates consisting of a fibrinogen derivative with a covalently bound anticancer drug seem to be a promising anticancer drug.
寻找治疗各类疾病，尤其是癌症相关疾病的新型创新方法，是制药公司和学术机构面临的一项挑战。使用含有广为人知且广泛应用的生物活性物质的缀合物是解决这一问题的途径之一。对药物与大分子载体系统结合的研究也加入到了寻找新治疗策略的行列中。
本文的主要目标是探讨使用纤维蛋白原衍生物作为抗白血病药物载体的潜力。分析了所得缀合物的物理化学性质，表征了相对于起始载体的变化，并分析了生物学意义。使用经腹腔（i.p.）接种的P388小鼠白血病模型进行体内研究。
开发了由共价结合抗癌药物的纤维蛋白原衍生物组成的缀合物。制定了载体的制备方法以及在水溶液中合成缀合物的方法，并对缀合物进行了纯化。研究表明，用FH-MTX缀合物治疗白血病小鼠的生存期确实明显长于未治疗动物（对照组）和用游离MTX治疗的小鼠。与未缀合的药物相比，观察到与水解纤维蛋白原缀合的MTX的抗白血病活性显著增加。报告的数据表明，水解纤维蛋白原可作为MTX药物的载体分子，以增强其抗白血病活性。
由共价结合抗癌药物的纤维蛋白原衍生物组成的缀合物似乎是一种有前景的抗癌药物。
