Jaracz Stanislav, Chen Jin, Kuznetsova Larisa V, Ojima Iwao
Department of Chemistry and Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Bioorg Med Chem. 2005 Sep 1;13(17):5043-54. doi: 10.1016/j.bmc.2005.04.084.
Traditional cancer chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be a killed by cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing severe undesirable side effects. Therefore, various drug delivery protocols and systems have been explored in the last three decades. Tumor cells overexpress many receptors and biomarkers, which can be used as targets to deliver cytotoxic agents into tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as 'prodrug', should be systemically non-toxic. This means that the linker must be stable in circulation. Upon internalization into the cancer cell the conjugate should be readily cleaved to regenerate the active cytotoxic agent. Tumor-targeting conjugates bearing cytotoxic agents can be classified into several groups based on the type of cancer recognition moieties. This review describes recent advances in tumor-targeting drug conjugates including monoclonal antibodies, polyunsaturated fatty acids, folic acid, hyaluronic acid, and oligopeptides as tumor-targeting moieties.
快速增殖的癌细胞更有可能被细胞毒性药物杀死。然而，实际上细胞毒性药物的特异性很低或几乎没有特异性，这会导致全身毒性，引发严重的不良副作用。因此，在过去三十年里人们探索了各种药物递送方案和系统。肿瘤细胞过度表达许多受体和生物标志物，这些可作为将细胞毒性药物递送至肿瘤的靶点。一般来说，肿瘤靶向药物递送系统由肿瘤识别部分和细胞毒性弹头组成，它们直接连接或通过合适的连接子相连形成缀合物。该缀合物可被视为“前药”，应在全身无毒。这意味着连接子在循环中必须稳定。缀合物内化进入癌细胞后应易于裂解以再生出活性细胞毒性药物。基于癌症识别部分的类型，携带细胞毒性药物的肿瘤靶向缀合物可分为几类。本综述描述了肿瘤靶向药物缀合物的最新进展，包括作为肿瘤靶向部分的单克隆抗体、多不饱和脂肪酸、叶酸、透明质酸和寡肽。
