Sobolev A S
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia.
J BUON. 2009 Sep;14 Suppl 1(Suppl 1):S33-42.
A major challenge in the development of specific and effective cancer treatments is the paradoxical situation that exploiting a molecular target that is accessible (surface membrane or extracellular matrix) is critical for achieving tumor selectivity whereas delivery of the therapeutic inside the cell, to the cell nucleus is generally required for maximizing the therapeutic effect. Photosensitizers, alpha-particle emitting radionuclides and foreign genetic material could be considered as such therapeutics if they possessed cellular and subcellular specificity. The author describes a novel approach of using modular recombinant transporters to target the therapeutics to the nucleus of cancer cells, where their action is most pronounced or can only be expressed. Photo-sensitizer-transporter conjugates displayed up to 3000 times greater efficacy than free photosensitizers and acquired cell specificity in contrast to free photosensitizers. Alpha-emitting radionuclides, conjugated with the modular transporters, acquired similar properties. DNA complexed with analogous transporters efficiently transfected target cells. The different modules of the transporters are interchangeable, meaning that they can be tailored for particular applications.
利用可及的分子靶点(表面膜或细胞外基质)对于实现肿瘤选择性至关重要,而通常需要将治疗剂递送至细胞内乃至细胞核以最大化治疗效果。如果光敏剂、发射α粒子的放射性核素和外源遗传物质具有细胞和亚细胞特异性,那么它们可被视为这类治疗剂。作者描述了一种使用模块化重组转运体将治疗剂靶向癌细胞核的新方法,在癌细胞核中它们的作用最为显著或只能在其中表达。与游离光敏剂相比,光敏剂 - 转运体缀合物的疗效高达游离光敏剂的3000倍,并且具有细胞特异性。与模块化转运体缀合的发射α粒子的放射性核素具有类似性质。与类似转运体复合的DNA可有效转染靶细胞。转运体的不同模块是可互换的,这意味着它们可针对特定应用进行定制。