Abstract The emergence of drug-resistant tumour cells significantly interferes with the effectiveness of chemotherapeutic treatment plans and represents a major obstacle in the ongoing quest to overcome cancers. Therefore, exploring in detail new therapeutic strategies that can obviate this important challenge is regarded as a very important topic at the time being. Herein, we propose a non-invasive and remotely controllable mechano-chemotherapeutic approach that relies on the use of a rotating magnetic field (RMF) of low intensity (45 m T) in combination with a therapeutic agent consisting of a composite nanomaterial comprised of a poly(lactic-co-glycolic acid) (PLGA) shell co-loaded with Zn0.2Fe2.8O4 magnetic nanoparticles (mNPs) and Doxorubicin (DOX). We show that RMF exposure induces a mechanical movement to this nanomaterial, which can be exploited for (i) controllably releasing the anti-cancer drug for chemotherapy, and (ii) promoting the death of tumour cells by means of mechanical forces exerted onto their membranes. Such dual behavior leads to combating cancer cells via different and complementary routes enabling a controllable and efficient therapy. The proposed model enables controllable tumor therapy by precisely operating the magnetic nanomaterials at the nanometer scale, and its applicability is neither restricted to the nanomaterial here demonstrated nor to solely addressing cancer. Modified variants of the proposed model, together with the corresponding therapeutic agents, can be developed to address other pathologies, enabling novel therapeutic approaches that exceed the precision and efficiency of current ones.

中文翻译：

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磁开关机械化学疗法通过克服耐药性来增强肿瘤细胞的死亡

摘要 耐药肿瘤细胞的出现显着干扰了化疗治疗计划的有效性，并代表了不断寻求克服癌症的主要障碍。因此，详细探索可以避免这一重要挑战的新治疗策略在目前被视为一个非常重要的课题。在此，我们提出了一种非侵入性和远程可控的机械化学治疗方法，该方法依赖于使用低强度 (45 m T) 的旋转磁场 (RMF) 与由复合纳米材料组成的治疗剂组合聚（乳酸 - 共 - 乙醇酸）（PLGA）壳与 Zn0.2Fe2.8O4 磁性纳米粒子（mNPs）和多柔比星（DOX）共载。我们表明，RMF 暴露会引起这种纳米材料的机械运动，可用于（i）可控地释放用于化疗的抗癌药物，以及（ii）通过施加在肿瘤细胞膜上的机械力促进肿瘤细胞的死亡。这种双重行为导致通过不同和互补的途径对抗癌细​​胞，从而实现可控和有效的治疗。所提出的模型通过在纳米尺度上精确操作磁性纳米材料来实现可控的肿瘤治疗，其适用性既不限于这里展示的纳米材料，也不限于仅用于治疗癌症。可以开发所提出模型的修改变体以及相应的治疗剂，以解决其他病理学问题，从而实现超越当前治疗方法精度和效率的新治疗方法。