Five year survival for metastatic melanoma (MM) is very low at <10%. Therapeutic options have been limited secondary to systemic toxicity. As a result there has been a growing movement towards developing targeted drug delivery models. Prior research of this group has demonstrated the effectiveness of acid-prepared mesoporous spheres (APMS-TEG) in delivering chemotherapeutic agents at a lower effective dose than systemic administration. This study aims to assess the ability of the previously developed APMS-TEG particles to deliver therapeutic doses of docetaxel for the treatment of melanoma. In vitro experiments were performed to assess docetaxel loading onto APMS-TEG particles and release kinetics. Toxicity experiments were performed using docetaxel and docetaxel loaded APMS-TEG. The effect on cell growth was assessed using the MelJuSo, UACC903, and WM1205 melanoma cell lines. Docetaxel demonstrated statistically significant dose dependent reduction in growth of melanoma cells. In all three cell lines, doses of 1 nM were sufficient to produce statistically significant reduction in cell growth. Scanning electron micrographs demonstrate increased uptake of APMS-TEG particles by melanoma cells in the first 24 hours, with the majority within the first 4 hours. Unloaded APMS particles had no effect on the melanoma cells, demonstrating that the particles themselves are not toxic. APMS-TEG particles had a peak release of drug within the first hour, with equilibration thereafter. The 5, 10, and 20 nM loaded particles all had statistically significant reduction in cell growth than the control groups. The high potency against melanoma cells makes docetaxel a suitable choice for loading into APMS-TEG particles. Docetaxel loaded APMS-TEG particles demonstrate significant activity against malignant melanoma and thus offer an innovative approach to the treatment of metastatic melanoma.

中文翻译：

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探索性地使用多西他赛负载酸制备的介孔球体治疗恶性黑色素瘤。

转移性黑色素瘤（MM）的五年生存率很低，仅为<10％。继全身毒性之后，治疗选择受到限制。结果，越来越有朝着开发靶向药物递送模型的运动。该组的先前研究已证明，酸制备的中孔球体（APMS-TEG）可以以比全身给药更低的有效剂量递送化学治疗剂。这项研究旨在评估先前开发的APMS-TEG颗粒递送多西他赛治疗剂量以治疗黑素瘤的能力。进行了体外实验以评估多西紫杉醇在APMS-TEG颗粒上的负载和释放动力学。使用多西紫杉醇和负载多西紫杉醇的APMS-TEG进行毒性实验。使用MelJuSo，UACC903和WM1205黑色素瘤细胞系评估对细胞生长的影响。多西紫杉醇显示出黑色素瘤细胞生长的统计学显着剂量依赖性降低。在所有三种细胞系中，1 nM的剂量足以在统计学上显着降低细胞生长。扫描电子显微照片显示，在最初的24小时内，黑色素瘤细胞对APMS-TEG颗粒的吸收增加，而大多数在最初的4小时内。卸载的APMS颗粒对黑素瘤细胞没有影响，表明该颗粒本身无毒。APMS-TEG颗粒在第一个小时内药物释放达到峰值，此后达到平衡。载有5、10和20 nM颗粒的细胞生长均较对照组明显减少。高抗黑素瘤细胞的能力使多西紫杉醇成为装载到APMS-TEG颗粒中的合适选择。装载多西他赛的APMS-TEG颗粒具有抗恶性黑色素瘤的显着活性，因此为转移性黑色素瘤的治疗提供了创新的方法。