Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5514-20. doi: 10.1016/j.bmcl.2011.06.101. Epub 2011 Jul 7.
We present here a general system for the coordination attachment of therapeutic proteins to a drug delivery system and its application in combined therapy. Proof of concept is demonstrated by the synthesis and testing of the targeted drug delivery system for cytostatics, which is based on a combination of the drug carrier Zn-porphyrin-cyclodextrin conjugates and their supramolecular coordination complexes with immunoglobulins. This system can be as readily used for a variety of therapeutic and targeting proteins including PAs, MAs, lectins, and HSA. Moreover, it allows combined photodynamic therapy, cell targeted chemotherapy and immunotherapy. When tested in a mouse model with human C32 carcinoma, the therapeutic superiority of the coordination assembly nanosystem was shown in comparison with the efficacy of building blocks used for the construction of the system.
我们在这里提出了一种将治疗性蛋白质协调附着到药物输送系统的通用系统,并将其应用于联合治疗中。通过合成和测试基于药物载体 Zn-卟啉-环糊精缀合物及其与免疫球蛋白的超分子配位复合物的细胞抑制剂靶向药物输送系统,证明了该概念的合理性。该系统可方便地用于多种治疗性和靶向性蛋白质,包括 PA、MA、凝集素和 HSA。此外,它还允许联合光动力疗法、细胞靶向化疗和免疫疗法。在具有人 C32 癌的小鼠模型中进行测试时,与用于构建该系统的构建块的功效相比,协调组装纳米系统的治疗优越性得到了证明。