Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074, Aachen, Germany.
BCMaterials, Bld. Martina Casiano, 3rd. Floor, UPV/EHU Science Park, 48940, Leioa, Spain.
Chem Soc Rev. 2022 Apr 4;51(7):2544-2582. doi: 10.1039/d1cs00468a.
Metal complexes are extensively used for cancer therapy. The multiple variables available for tuning (metal, ligand, and metal-ligand interaction) offer unique opportunities for drug design, and have led to a vast portfolio of metallodrugs that can display a higher diversity of functions and mechanisms of action with respect to pure organic structures. Clinically approved metallodrugs, such as cisplatin, carboplatin and oxaliplatin, are used to treat many types of cancer and play prominent roles in combination regimens, including with immunotherapy. However, metallodrugs generally suffer from poor pharmacokinetics, low levels of target site accumulation, metal-mediated off-target reactivity and development of drug resistance, which can all limit their efficacy and clinical translation. Nanomedicine has arisen as a powerful tool to help overcome these shortcomings. Several nanoformulations have already significantly improved the efficacy and reduced the toxicity of (chemo-)therapeutic drugs, including some promising metallodrug-containing nanomedicines currently in clinical trials. In this critical review, we analyse the opportunities and clinical challenges of metallodrugs, and we assess the advantages and limitations of metallodrug delivery, both from a nanocarrier and from a metal-nano interaction perspective. We describe the latest and most relevant nanomedicine formulations developed for metal complexes, and we discuss how the rational combination of coordination chemistry with nanomedicine technology can assist in promoting the clinical translation of metallodrugs.
金属配合物在癌症治疗中得到广泛应用。多种可调变量（金属、配体和金属-配体相互作用）为药物设计提供了独特的机会，并产生了大量的金属药物，与纯有机结构相比，这些金属药物具有更高的功能多样性和作用机制。临床批准的金属药物，如顺铂、卡铂和奥沙利铂，用于治疗多种类型的癌症，并在联合治疗方案中发挥重要作用，包括与免疫疗法联合。然而，金属药物通常存在较差的药代动力学、靶部位积累水平低、金属介导的脱靶反应和耐药性发展等问题，这些都可能限制其疗效和临床转化。纳米医学已成为克服这些缺点的有力工具。几种纳米制剂已经显著提高了（化疗）治疗药物的疗效并降低了其毒性，包括一些有前途的含金属药物的纳米药物目前正在临床试验中。在这篇评论中，我们分析了金属药物的机遇和临床挑战，并从纳米载体和金属-纳米相互作用的角度评估了金属药物传递的优势和局限性。我们描述了为金属配合物开发的最新和最相关的纳米医学制剂，并讨论了如何将配位化学与纳米医学技术合理结合，以促进金属药物的临床转化。
