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首页> 外文期刊>Nanotechnology >Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma
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Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma

机译：单壁碳纳米管共轭化学疗法在黑素瘤中显示出更高的治疗指数

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摘要

The incidence of malignant melanoma is increasing at an alarming rate globally. Poor prognosis and extraordinarily low survival rates of malignant melanoma necessitates the development of new chemotherapeutic strategies. An emerging approach is to harness nanotechnology to optimize the existing chemotherapies. In the present study we have demonstrated that the delivery of doxorubicin using a nanotechnology-based platform significantly reduces the systemic toxicity of the drug, keeping unchanged its therapeutic efficacy in a mouse melanoma tumor model. Specifically we modified single-walled carbon nanotubes (CNTs) to conjugate a doxorubicin prodrug via a carbamate linker that cleaves enzymatically to cause temporal release of the active drug. The CNT-doxorubicin conjugate (CNT-Dox) induced time-dependent cell death in B16-F10 melanoma cells in vitro. The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. Our studies demonstrate that a simple and versatile CNT-based nanovector can be harnessed for the delivery of chemotherapy to melanoma, with increased therapeutic index.
机译：全球恶性黑色素瘤的发病率正以惊人的速度增加。恶性黑色素瘤的不良预后和极低的存活率需要开发新的化学治疗策略。一种新兴的方法是利用纳米技术来优化现有的化学疗法。在本研究中，我们已经证明，使用基于纳米技术的平台递送阿霉素可显着降低药物的全身毒性，而在小鼠黑素瘤肿瘤模型中保持其治疗功效不变。具体来说，我们修改了单壁碳纳米管（CNTs），以通过氨基甲酸酯连接物偶联阿霉素前药，该连接物会酶促裂解，从而导致活性药物的暂时释放。 CNT-阿霉素结合物（CNT-Dox）在体外诱导B16-F10黑色素瘤细胞的时间依赖性细胞死亡。纳米粒子被快速内化到黑色素瘤细胞的溶酶体中，并在亚细胞区室中保留了超过24小时。在体内黑素瘤模型中，用纳米管-阿霉素结合物治疗可消除肿瘤生长，而没有与游离阿霉素相关的全身性副作用。我们的研究表明，可以利用简单且通用的基于CNT的纳米载体将化学疗法递送至黑色素瘤，并提高治疗指数。

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