Mallikaratchy Prabodhika, Tang Zhiwen, Tan Weihong
Department of Chemistry, University of Florida, Center for Research at Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
ChemMedChem. 2008 Mar;3(3):425-8. doi: 10.1002/cmdc.200700260.
This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition, we will be able to develop highly efficient photosensitizer based therapeutical reagents for clinical applications.
本文描述了一种将光敏剂与适配体的分子构建体应用于光疗靶向肿瘤细胞的方法。提高化疗药物选择性的关键步骤是创建能够靶向癌细胞而非正常细胞的有效分子平台。最近,我们通过细胞SELEX(指数富集配体系统进化)开发了一种策略,以完整活细胞为靶点获得细胞特异性适配体,从而筛选出能够以高选择性和优异亲和力识别细胞膜蛋白的适配体。我们已经鉴定出一种仅识别伯基特淋巴瘤细胞系Ramos细胞的适配体TD05。在此,将适配体在靶细胞结合方面的高特异性与一种高效光疗试剂Ce6进行分子工程改造,构建出一种高选择性的适配体-光敏剂缀合物(APS),以有效破坏靶癌细胞。引入APS缀合物后再进行光照,可选择性地破坏靶Ramos细胞,而不会影响急性淋巴细胞白血病和髓系白血病细胞系。这项研究表明,将癌症特异性适配体与光敏剂缀合使用将提高光动力疗法的选择性。结合细胞SELEX在生成多种用于识别病变细胞的有效适配体方面的优势,我们将能够开发出高效的基于光敏剂的治疗试剂用于临床应用。