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Limiting tumor cells comprehensively at micro and macro levels to improve the therapeutic effect of chemotherapy

机译：在微观和宏观水平综合限制肿瘤细胞，以改善化疗的治疗效果

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Clinical data shows that antitumor treatments are often ineffective if tumor cells have metastasized. To gain an effective antitumor therapeutic effect, in this report, the tumor cell was limited to the primary site and simultaneously ablated by chemotherapy. Considering the extremely complicated process of cancer metastasis, we seek to comprehensively suppress tumor metastases at both micro and macro levels, which closely link to migration and interact with each other. At the micro level, the motility of the tumor cell was decreased via accelerating mitochondria fusion. At the macro level, the unfavorable hypoxia environment was improved. A liposome-based multifunctional nanomedicine was designed by coloading latrunculin B (LAT-B), an inhibitor of actin polymerization, and doxorubicin (DOX) into the hydrophobic bilayers and aqueous cavity, respectively. Meanwhile, an oxygen reservoir named perfluoropentane (PFP) was encapsulated into the liposome core to fulfill synergistic treatment of metastatic tumors. In this paper, we demonstrated that the metastasis of the tumor cell could be effectively inhibited by LAT-B through promoting mitochondria fusion without affecting its function, making it as an encouraging candidate for effective anti-metastasis therapy. Meanwhile, we found that the combination of LAT-B and DOX shows a synergistic effect against tumors because the combined effect of these two drugs cover the entire cell proliferation process. In a word, this report presents a potential improvement in the treatment of metastatic cancer.
机译：临床数据表明，如果肿瘤细胞转移，抗肿瘤治疗通常无效。为了获得有效的抗肿瘤治疗效果，在本报告中，肿瘤细胞被限制在原发部位，同时通过化疗进行消融。考虑到癌症转移过程极其复杂，我们寻求在微观和宏观层面上全面抑制肿瘤转移，这与迁移密切相关，并且相互影响。在微观层面，肿瘤细胞的运动性通过加速线粒体融合而降低。在宏观层面，改善了不利的缺氧环境。通过将肌动蛋白聚合抑制剂latrunculin B（LAT-B）和阿霉素（DOX）分别与疏水性双层膜和水腔共载，设计了一种基于脂质体的多功能纳米药物。同时，将名为全氟戊烷（PFP）的储氧器封装到脂质体核心中，以实现对转移性肿瘤的协同治疗。在本文中，我们证明了LAT-B可以通过促进线粒体融合而有效地抑制肿瘤细胞的转移，而不影响其功能，使其成为有效抗转移治疗的令人鼓舞的候选者。同时，我们发现，LAT-B和DOX的联合使用对肿瘤具有协同作用，因为这两种药物的联合作用覆盖了整个细胞增殖过程。总之，这份报告展示了转移癌治疗的潜在改进。

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