Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma
Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma
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DOI：
10.1088/0957-4484/21/2/025102
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发表时间：
2010-01-15
期刊：
影响因子：
3.5
通讯作者：
Sengupta, Shiladitya
中科院分区：
文献类型：
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作者：
Chaudhuri, Padmaparna;Soni, Shivani;Sengupta, Shiladitya
恶性黑色素瘤的发病率在全球范围内以惊人的速度增加。恶性黑色素瘤预后差，生存率极低，需要开发新的化疗策略。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多柔比星显着降低了药物的全身毒性，保持其在小鼠黑色素瘤肿瘤模型中的治疗功效不变。具体来说，我们修改单壁碳纳米管（CNT）共轭阿霉素前药通过氨基甲酸酯连接器，酶促裂解，导致临时释放的活性药物。CNT-阿霉素缀合物（CNT-Dox）在体外诱导B16-F10黑色素瘤细胞中的时间依赖性细胞死亡。纳米颗粒被迅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超过24小时。在体内黑色素瘤模型中，用纳米管-多柔比星缀合物治疗消除了肿瘤生长，而没有与游离多柔比星相关的全身副作用。我们的研究表明，一种简单而通用的基于CNT的纳米载体可以用于向黑色素瘤递送化疗，并具有增加的治疗指数。
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.