Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt.
Pharmacology Department, Faculty of Medicine, Ain Shams University, Egypt.
Biomed Pharmacother. 2017 Nov;95:1209-1218. doi: 10.1016/j.biopha.2017.09.059. Epub 2017 Sep 18.
In metastatic breast cancer (MBC), the conventional doxorubicin (DOX) has various problems due to lack of selectivity with subsequent therapeutic failure and adverse effects. DOX- induced cardiotoxicity is a major problem that necessitates the presence of new forms to decrease the risk of associated morbidity. Nanoparticles (NPs) are considered an important approach to selectively increase drug accumulation inside tumor cells and thus decreasing the associated side effects. Tumor cells develop resistance to chemotherapeutic agents through multiple mechanisms, one of which is over expression of efflux transporters. Various NPs have been investigated to overcome efflux mediated resistance. To date, only liposomal doxorubicin (LD) and pegylated liposomal doxorubicin (PLD) have entered phase II and III clinical trials and FDA- approved for clinical use in MBC. This review addresses the effects of LD and PLD on the hematological and palmar-plantar erythrodysesthesia (PPE) in anthracycline naïve and pretreated MBC patients. For evidence, studies to be included in this review were identified through PubMed, Cochrane and Google scholar databases. The results derived from: four phase III clinical trials that compared LD with the conventional DOX in naïve MBC patients, and ten non-comparative clinical trials investigated LD and PLD as monotherapy or combination in pretreated MBC. This work confirmed the cardiac tolerability profile of LD and PLD versus DOX, while hematological and skin toxicities were more common. Other DOX-NPs in preclinical trials were discussed in a chronological order. Finally, the modern preclinical development framework for DOX includes exosomal DOX (exo-DOX). Exosomal NPs are non-toxic, non-immunogenic, and can be engineered to have high cargo loading capacity and targeting specificity. These NPs have not been investigated clinically. Our study shows that the full clinical potentiality of DOX-NPs remains to be addressed to move the field forward.
在转移性乳腺癌 (MBC) 中，由于缺乏选择性，常规阿霉素 (DOX) 会导致随后的治疗失败和不良反应等各种问题。DOX 诱导的心脏毒性是一个主要问题，需要采用新的形式来降低相关发病率的风险。纳米颗粒 (NPs) 被认为是一种重要的方法，可以选择性地增加肿瘤细胞内药物的积累，从而降低相关的副作用。肿瘤细胞通过多种机制对化疗药物产生耐药性，其中之一是外排转运蛋白的过度表达。已经研究了各种 NPs 来克服外排介导的耐药性。迄今为止，只有脂质体阿霉素 (LD) 和聚乙二醇化脂质体阿霉素 (PLD) 已进入 II 期和 III 期临床试验，并获得 FDA 批准用于 MBC 的临床应用。这篇综述讨论了 LD 和 PLD 对初治和预处理 MBC 患者血液学和掌跖红细胞发育不良 (PPE) 的影响。为了证明这一点，通过 PubMed、Cochrane 和 Google Scholar 数据库确定了本综述中包含的研究。结果来自：四项比较 LD 与初治 MBC 患者常规 DOX 的 III 期临床试验，以及十项非对照临床试验研究了 LD 和 PLD 作为单药或联合治疗预处理 MBC。这项工作证实了 LD 和 PLD 与 DOX 相比具有心脏耐受性，而血液学和皮肤毒性更为常见。还按时间顺序讨论了其他处于临床前试验阶段的 DOX-NPs。最后，DOX 的现代临床前开发框架包括外泌体 DOX (exo-DOX)。外泌体 NPs 无毒、无免疫原性，可以设计成具有高载药能力和靶向特异性。这些 NPs 尚未在临床上进行研究。我们的研究表明，DOX-NPs 的全部临床潜力仍有待解决，以推动该领域的发展。
