Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
Faculty of Pharmacy, Research Institute for Medicines, iMed.ULisboa, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
Drug Deliv Transl Res. 2022 Jan;12(1):49-66. doi: 10.1007/s13346-021-00916-7. Epub 2021 Feb 22.
Worldwide, colon cancer (CC) represents the fourth most common type of cancer and the fifth major cause of cancer-associated deaths. Surgical resection is considered the standard therapeutic choice for CC in early stages. However, in latter stages of the disease, adjuvant chemotherapy is essential for an appropriate management of this pathology. Metal-based complexes displaying cytotoxic properties towards tumor cells emerge as potential chemotherapeutic options. One metallodrug, oxaliplatin, was already approved for clinical use, playing an important role in the treatment of CC patients. Unfortunately, most of the newly designed metal-based complexes exhibit lack of selectivity against cancer cells, low solubility and permeability, high dose-limiting toxicity, and emergence of resistances. Nanodelivery systems enable the incorporation of metallodrugs at adequate payloads, solving the above-referred drawbacks. Moreover, drug delivery systems, depending on their physicochemical properties, are able to release the incorporated material preferentially at affected tissues/organs, enhancing the therapeutic activity in vivo, with concomitant fewer side effects. In this review, the general features and therapeutic management of CC will be addressed, with a special focus on preclinical or clinical studies using metal-based compounds. Furthermore, the use of different nanodelivery systems will also be described as tools to potentiate the therapeutic index of metallodrugs for the management of CC.
在全球范围内,结肠癌 (CC) 是第四大常见癌症类型,也是癌症相关死亡的第五大主要原因。手术切除被认为是早期 CC 的标准治疗选择。然而,在疾病的晚期,辅助化疗对于这种疾病的适当管理是必不可少的。具有细胞毒性的基于金属的配合物作为潜在的化疗选择出现。一种金属药物奥沙利铂已被批准用于临床,在治疗 CC 患者方面发挥着重要作用。不幸的是,大多数新设计的基于金属的配合物对癌细胞缺乏选择性,溶解度和渗透性低,剂量限制毒性高,并且出现耐药性。纳米递药系统能够以适当的载药量将金属药物掺入其中,解决了上述缺点。此外,根据其物理化学性质,药物递送系统能够优先将所包含的物质释放到受影响的组织/器官中,在体内增强治疗活性,同时减少副作用。在这篇综述中,将讨论 CC 的一般特征和治疗管理,特别关注使用基于金属的化合物的临床前或临床研究。此外,还将描述不同的纳米递药系统作为增强金属药物治疗 CC 的治疗指数的工具。