Department of Chemistry, Amity Institute of Applied Sciences, Amity University, Action Area-II, Kadampukur, New Town, Rajarhat, Kolkata 700135, India.
Department of Chemistry, Amity Institute of Applied Sciences, Amity University, Action Area-II, Kadampukur, New Town, Rajarhat, Kolkata 700135, India; Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France.
Bioorg Med Chem. 2024 Oct 1;112:117894. doi: 10.1016/j.bmc.2024.117894. Epub 2024 Aug 23.
Platinum-based anticancer drugs have been at the forefront of cancer chemotherapy, with cisplatin emerging as a pioneer in the treatment of various malignancies. This review article provides a comprehensive overview of the evolution of platinum-based anticancer therapeutics, focusing on the development of cisplatin, platinum(IV) prodrugs, and the integration of photodynamic therapy (PDT) for enhanced cancer treatment results. The first section of the review delves into the historical context and molecular mechanisms underlying the success of cisplatin, highlighting its DNA binding properties and subsequent interference with cellular processes. Despite its clinical efficacy, the inherent limitations, including dose-dependent toxicities and acquired resistance, accelerated the exploration of novel platinum derivatives. This led to the emergence of platinum(IV) prodrugs, designed to overcome resistance mechanisms and enhance selectivity through targeted drug delivery. The subsequent section provides an in-depth analysis of the principles of design and structural modifications employed in the development of platinum(IV) prodrugs. The transitions to the incorporation of photodynamic therapy (PDT) stands out as a synergistic approach to platinum-based anticancer treatment. The photophysical properties of platinum complexes are discussed in the context of their potential application in PDT, emphasizing on combined cytotoxic effects of platinum-based drugs and light-induced reactive oxygen species generation. This dual-action approach holds great promise for overcoming the limitations of traditional chemotherapy as well as producing superior therapeutic outcomes. Overall, the present report explores the latest developments in the development and use of platinum complexes, highlighting novel strategies such combination treatments, targeted delivery methods, and the generation of multifunctional complexes. It also provides a comprehensive overview of the current landscape while proposing future directions for the development of next-generation platinum-based anticancer therapeutics.
铂类抗癌药物一直处于癌症化疗的前沿,顺铂作为治疗各种恶性肿瘤的先驱药物脱颖而出。本文综述了铂类抗癌治疗药物的发展历程,重点介绍了顺铂、铂(IV)前药以及光动力疗法(PDT)的整合,以提高癌症治疗效果。本文首先探讨了顺铂成功的历史背景和分子机制,强调了其与 DNA 的结合特性以及对细胞过程的后续干扰。尽管顺铂具有临床疗效,但由于其剂量依赖性毒性和获得性耐药性等固有局限性,促使人们加速探索新型铂类衍生物。这导致了铂(IV)前药的出现,旨在通过靶向药物递送克服耐药机制并提高选择性。接下来深入分析了铂(IV)前药设计和结构修饰的原理。随后将光动力疗法(PDT)的引入作为一种协同的铂类抗癌治疗方法。讨论了铂配合物的光物理性质及其在 PDT 中的潜在应用,强调了铂类药物与光诱导的活性氧生成的联合细胞毒性作用。这种双重作用方法有望克服传统化疗的局限性,产生更好的治疗效果。总的来说,本报告探讨了铂类配合物的开发和应用的最新进展,强调了联合治疗、靶向递送方法和多功能配合物的生成等新策略。同时,本文还对当前的研究现状进行了全面概述,并提出了下一代铂类抗癌治疗药物的未来发展方向。