Background: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging.
Purpose: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality.
Methods and Results: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis.
Conclusion: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.



中文翻译：

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基于薯蓣皂苷元的 pH 敏感前药纳米载体，用于递送阿霉素以有效抑制肿瘤转移。


背景：转移是癌症治疗的最大障碍之一，是肿瘤恶化和复发的主要原因。抗转移已被认为是临床癌症管理的可行策略。众所周知，薯蓣皂苷元可以抑制肿瘤转移，阿霉素（DOX）可以诱导肿瘤细胞凋亡。然而，它们的高效交付仍然具有挑战性。

目的：为了解决这些问题，开发了一种基于薯蓣皂苷元纳米颗粒（NPs）平台的新型pH敏感聚合物前药，以提高DOX递送（DOX/NPs）的效率，用于协同治疗皮肤黑色素瘤（最致命的皮肤形式）癌症恶性程度高、转移早、死亡率高。

方法与结果： DOX/NPs对肿瘤增殖和迁移的抑制作用优于NPs或游离DOX。更重要的是，DOX/NPs可以将线粒体相关的转移和细胞凋亡与载体独特的内化途径结合起来对抗肿瘤。此外，生物分布实验证明，与游离DOX相比，DOX/NPs可以通过增强渗透和滞留（EPR）效应在肿瘤部位有效积累。重要的是，体内实验数据表明，无心脏毒性的DOX/NPs通过发挥协同治疗作用显着抑制肿瘤转移，并通过诱导细胞凋亡来减少肿瘤体积和重量。

结论：基于两种不同功能药物的建立，具有令人满意的药学特性的纳米载体DOX/NPs是协同增强癌症治疗效果的有前途的策略。