Rahman Atiar M, Yusuf Syed Wamique, Ewer Michael S
Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Int J Nanomedicine. 2007;2(4):567-83.
The anthracyclines are a group of antibiotics that are among the most potent chemotherapeutic agents. They are highly effective against a broad spectrum of malignancies, including lymphoma, gastric cancer, small cell lung cancer, sarcoma, and breast cancer. Unfortunately, these agents also exhibit a well-recognized cumulative-dose related cardiotoxic profile that limits the extent to which they can be used safely. In clinical practice, most clinicians limit the cumulative dose of doxorubicin (the most widely used agent in this group) to 400-450 mg/m2, but considerable cardiac damage is now known to occur at cumulative dosages considerably below this level. Regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. The application of nanotechnology to medicine involves the use of devices that will interact with the body at the molecular level. These methods can lead to target and tissue specific clinical application, often with minimal or reduced side effects. Liposomal preparations incorporate such technology, thereby altering some important characteristics of the parent compound and facilitating concentration at the tumor site. In the case of liposomal doxorubicin, cardiotoxicity is reduced significantly. This review summarizes the important information on the liposomal preparation of anthracyclines.
蒽环类药物是一类抗生素,属于最有效的化疗药物。它们对多种恶性肿瘤具有高度疗效,包括淋巴瘤、胃癌、小细胞肺癌、肉瘤和乳腺癌。不幸的是,这些药物也表现出一种公认的与累积剂量相关的心脏毒性特征,这限制了它们安全使用的程度。在临床实践中,大多数临床医生将阿霉素(该类中使用最广泛的药物)的累积剂量限制在400 - 450mg/m²,但现在已知在远低于该水平的累积剂量下也会发生相当程度的心脏损伤。使用新型联合药物方案(其中研究最广泛的是单克隆抗体曲妥珠单抗)已知会增强蒽环类药物的心脏毒性。纳米技术在医学上的应用涉及使用在分子水平与身体相互作用的装置。这些方法可导致靶向和组织特异性的临床应用,通常副作用最小或减少。脂质体制剂采用了此类技术,从而改变了母体化合物的一些重要特性,并促进其在肿瘤部位的聚集。就脂质体阿霉素而言,心脏毒性显著降低。本综述总结了蒽环类药物脂质体制剂的重要信息。