Gao Yu, Tang Mingtan, Leung Euphemia, Svirskis Darren, Shelling Andrew, Wu Zimei
School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland Auckland 1142 New Zealand
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland Auckland 1023 New Zealand.
RSC Adv. 2020 May 19;10(32):19089-19105. doi: 10.1039/d0ra02801k. eCollection 2020 May 14.
Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse. BCSCs are difficult to eradicate due to their high resistance to conventional treatments and high plasticity. Functionalised nanoparticles have been investigated as smart vehicles to transport across various barriers and increase the interaction of therapeutic agents with cancer cells, as well as BCSCs. In this review, we discuss the different characteristics of BCSCs, and challenges to tackle BCSCs at cellular and molecular levels. The mechanisms of action and physicochemical properties of the current BCSC targeting agents are also covered. We will focus on the rational design and recent advances of "Nano + Nano" or single tumour targeting nanoparticle systems loaded with dual or multiple agents to kill all cancer cells including BCSCs. These cocktail therapies include the combination of a chemotherapy agent with a BCSC-specific inhibitor, a phytochemical agent or RNA based therapy. Given the heterogeneity of breast tumour tissue, targeting both BCSCs and bulk breast cancer cells simultaneously with multiple agents holds great promise in eliminating breast cancer. The future research needs to focus on overcoming various barriers in the 'clinical translation' of BCSC-targeting nanomedicines to cure breast cancer, which requires a significant multidisciplinary effort.
乳腺癌干细胞（BCSCs）已被发现与治疗抗性和疾病复发有关。由于BCSCs对传统治疗具有高抗性和高可塑性，因此难以根除。功能化纳米颗粒已被研究作为智能载体，用于跨越各种屏障并增加治疗剂与癌细胞以及BCSCs的相互作用。在这篇综述中，我们讨论了BCSCs的不同特征，以及在细胞和分子水平上应对BCSCs的挑战。还涵盖了当前BCSC靶向剂的作用机制和物理化学性质。我们将重点关注负载双药或多药以杀死包括BCSCs在内的所有癌细胞的“纳米+纳米”或单肿瘤靶向纳米颗粒系统的合理设计和最新进展。这些联合疗法包括化疗药物与BCSC特异性抑制剂、植物化学药物或基于RNA的疗法的组合。鉴于乳腺肿瘤组织的异质性，用多种药物同时靶向BCSCs和乳腺癌细胞在消除乳腺癌方面具有很大的前景。未来的研究需要专注于克服BCSC靶向纳米药物“临床转化”中的各种障碍以治愈乳腺癌，这需要多学科的巨大努力。
