Singh Vimal K, Saini Abhishek, Chandra Ramesh
Stem Cell Research Laboratory, Department of Biotechnology, Delhi Technological UniversityNew Delhi, India.
Department of Chemistry, University of DelhiNew Delhi, India.
Front Mol Biosci. 2017 Jul 21;4:52. doi: 10.3389/fmolb.2017.00052. eCollection 2017.
Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs. In recent years, many reports have shown the use of CSCs-specific approaches such as ATP-binding cassette (ABC) transporters, blockade of self-renewal and survival of CSCs, CSCs surface markers targeted drugs delivery and eradication of the tumor microenvironment. Also, various therapeutic agents such as small molecule drugs, nucleic acids, and antibodies are said to destroy CSCs selectively. Targeted drug delivery holds the key to the success of most of the anti-CSCs based drugs/therapies. The convention CSCs-specific therapeutic agents, suffer from various problems. For instance, limited water solubility, small circulation time and inconsistent stability of conventional therapeutic agents have significantly limited their efficacy. Recent advancement in the drug delivery technology has demonstrated that specially designed nanocarrier-based drug delivery approaches (nanomedicine) can be useful in delivering sufficient amount of drug molecules even in the most interiors of CSCs niches and thus can overcome the limitations associated with the conventional free drug delivery methods. The nanomedicine has also been promising in designing effective therapeutic regime against pump-mediated drug resistance (ATP-driven) and reduces detrimental effects on normal stem cells. Here we focus on the biological processes regulating CSCs' drug resistance and various strategies developed so far to deal with them. We also review the various nanomedicine approaches developed so far to overcome these CSCs related issues and their future perspectives.
癌症干细胞(CSCs)被认为具有独特的自我更新、增殖和分化能力,因此在癌症的各个方面都发挥着重要作用。CSCs对不同类型恶性肿瘤的肿瘤进展、耐药性、复发和转移具有重大影响。由于其主要作用,大多数研究人员专注于开发抗CSC治疗策略,并付出了巨大努力来探索选择性根除这些具有治疗抗性的CSCs的方法。近年来,许多报告显示了使用CSCs特异性方法,如ATP结合盒(ABC)转运蛋白、阻断CSCs的自我更新和存活、靶向CSCs表面标志物的药物递送以及消除肿瘤微环境。此外,据说各种治疗剂,如小分子药物、核酸和抗体,能够选择性地破坏CSCs。靶向药物递送是大多数基于抗CSCs的药物/疗法成功的关键。传统的CSCs特异性治疗剂存在各种问题。例如,传统治疗剂的水溶性有限、循环时间短和稳定性不一致,显著限制了它们的疗效。药物递送技术的最新进展表明,专门设计的基于纳米载体的药物递送方法(纳米医学)即使在CSCs生态位的最内部也能有效地递送足够数量的药物分子,从而可以克服与传统游离药物递送方法相关的局限性。纳米医学在设计针对泵介导的耐药性(ATP驱动)的有效治疗方案以及减少对正常干细胞的有害影响方面也很有前景。在这里,我们关注调节CSCs耐药性的生物学过程以及迄今为止开发的各种应对策略。我们还回顾了迄今为止为克服这些与CSCs相关的问题而开发的各种纳米医学方法及其未来前景。