Trubetskoy V S, Berdichevsky V R, Efremov E E, Torchilin V P
Biochem Pharmacol. 1987 Mar 15;36(6):839-42. doi: 10.1016/0006-2952(87)90172-9.
In order to make the drug targeting system more effective, simple and technological, we suggest creation of drug-bearing conjugates capable of simultaneous binding with different antigenic components of the target via specific antibodies. It is supposed that the targeted therapy should include sequential administration of the mixture of modified antibodies (or other specific vectors) against different components of affected tissue and, upon antibody accumulation in the desired region, administration of modified drugs or drug carrying systems which can recognize and bind with the target via accumulated antibodies due to the interaction between vector modifier and carrier modifier. Using as a model system monolayers consisting of the mixture of extracellular antigens and appropriated antibodies, it was shown that the treatment of the target with the mixture of biotinylated antibodies against all target components and subsequent binding with the target of biotinylated liposomes via avidin permits high liposome accumulation on the monolayer. The binding achieved is always higher than in the case of the utilization of single antibody-bearing liposomes. Besides, the system suggested is very simple and its components can be easily obtained on technological scale in standardized conditions.
为了使药物靶向系统更有效、更简单且更具技术性，我们建议创建能够通过特异性抗体与靶标的不同抗原成分同时结合的载药缀合物。据推测，靶向治疗应包括针对受影响组织的不同成分依次施用修饰抗体（或其他特异性载体）的混合物，并且在抗体在所需区域积累后，施用能够通过载体修饰剂与载体修饰剂之间的相互作用，经由积累的抗体识别并结合靶标的修饰药物或载药系统。以由细胞外抗原和合适抗体的混合物组成的单层作为模型系统，结果表明，用针对所有靶标成分的生物素化抗体混合物处理靶标，随后通过抗生物素蛋白使生物素化脂质体与靶标结合，可使脂质体在单层上大量积累。所实现的结合始终高于使用单抗体脂质体的情况。此外，所建议的系统非常简单，其成分可以在标准化条件下在技术规模上轻松获得。
