Mazloomi MirAhmad, Doustmihan Abolfazl, Alimohammadvand Sajjad, Hamishehkar Hamed, Hamblin Michael R, Jahanban Esfahlan Rana
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 5166614733, Iran.
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 5166614733, Iran.
Asian J Pharm Sci. 2025 Jun;20(3):101036. doi: 10.1016/j.ajps.2025.101036. Epub 2025 Feb 19.
Cancer stem cells (CSCs) are a major challenge in cancer therapy. Stem cell-like cells form a unique subpopulation within many tumors, which govern the degree of malignancy by promoting metastasis, recurrence, heterogeneity, and resistance to drug and radiation. Furthermore, these cells can persist in patients even after undergoing multiple cycles of conventional cancer therapy via dormancy, where they no longer dividing but remain active. These may cause cancer recurrence at any time, even years after a supposed cure, and remain invisible to the immune system. Targeting specific surface markers, signaling pathways and tumor microenvironment, which all have a significant effect on CSC function and maintenance, could help to eradicate CSCs and improve patient survival. Combinations of traditional therapies with nano-based drug delivery systems can efficiently target CSCs. Considering the biology and properties of CSCs, we classify recent approaches involving nanoparticle engineering, extracellular matrix modulation, cocktail strategies, multi-stage therapy, CSC defanging, Trojan horse systems, targeted therapy and organelle targeting. We highlight the most recent advances in nanocarrier design and drug delivery technologies to target CSCs, combined with conventional treatment in preclinical and clinical trials. The prospects of these approaches for CSCs elimination and recurrent cancer treatment are discussed.
癌症干细胞（CSCs）是癌症治疗中的一个重大挑战。干细胞样细胞在许多肿瘤中形成一个独特的亚群，通过促进转移、复发、异质性以及对药物和辐射的抗性来控制恶性程度。此外，即使在经历多个周期的传统癌症治疗后，这些细胞也可通过休眠在患者体内持续存在，在此状态下它们不再分裂但仍保持活性。这些细胞可能在任何时候导致癌症复发，甚至在假定治愈多年后仍会复发，并且对免疫系统不可见。靶向对CSC功能和维持有重大影响的特定表面标志物、信号通路和肿瘤微环境，可能有助于根除CSCs并提高患者生存率。传统疗法与基于纳米的药物递送系统相结合可以有效地靶向CSCs。考虑到CSCs的生物学特性，我们对涉及纳米颗粒工程、细胞外基质调节、联合策略、多阶段疗法、CSC去功能化、特洛伊木马系统、靶向疗法和细胞器靶向的最新方法进行了分类。我们重点介绍了在临床前和临床试验中，纳米载体设计和药物递送技术与传统治疗相结合以靶向CSCs的最新进展。讨论了这些方法在消除CSCs和治疗复发性癌症方面的前景。
