Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
1] Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA [2] Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, California, USA.
Mol Ther Nucleic Acids. 2014 Jun 17;3(6):e169. doi: 10.1038/mtna.2014.21.
One hundred years ago, Dr. Paul Ehrlich popularized the "magic bullet" concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, "targeted therapy" that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.
一百年前，保罗·埃尔利希（Paul Ehrlich）博士将“魔弹”概念普及用于癌症治疗，即理想的治疗剂仅杀死其靶向的特定肿瘤细胞。从那时起，针对导致患者疾病的分子缺陷的“靶向治疗”就成为治疗人类疾病的长期目标。然而，在癌症和传染病的治疗过程中，安全有效的药物输送仍然是临床转化和新疗法开发的主要挑战。SELEX 技术的出现激发了许多开创性的研究，这些研究成功地将细胞特异性适体适应于体外和体内模型中活性药物物质的靶向传递。通过将细胞特异性适体与治疗剂（如 siRNA、microRNA、化疗药物或毒素）或递药载体（如有机或无机纳米载体）共价连接或物理功能化，可特异性识别靶向细胞和组织，并将治疗化合物内化，从而提高药物的局部浓度和治疗效果。目前，已经开发出许多针对不同疾病或组织的细胞类型特异性适体，本文将讨论细胞特异性适体在靶向疾病治疗中的最新进展，以及偶联策略和挑战。
