Dacarbazine-Loaded Hollow Mesoporous Silica Nanoparticles Grafted with Folic Acid for Enhancing Antimetastatic Melanoma Response
Dacarbazine-Loaded Hollow Mesoporous Silica Nanoparticles Grafted with Folic Acid for Enhancing Antimetastatic Melanoma Response
复制标题
负载达卡巴嗪的空心介孔二氧化硅纳米粒子接枝叶酸以增强抗转移性黑色素瘤反应
DOI：
10.1021/acsami.7b05278
复制
发表时间：
2017-07-05
影响因子：
9.5
通讯作者：
Tao, Juan
中科院分区：
文献类型：
--
作者：
Liu, Qianqian;Xu, Nan;Tao, Juan
达卡巴嗪（Dacarbazine，DTIC）是治疗黑色素瘤的重要化疗药物之一，但其溶解性差、光敏性差、不稳定、对正常细胞毒性大等缺点限制了其临床应用。在这篇文章中，我们提出了一个合理设计的纳米载体的基础上中空介孔二氧化硅纳米粒子（HMSNs）的包封和靶向释放DTIC根除黑色素瘤。通过修饰制备了纳米载体（DTIC@HMLBFs）。HMSNs与羧基，以提高负载DTIC，随后进一步包封叶酸接枝的脂质体，这作为一个黑色素瘤的活性靶标，控制和靶向药物释放。在体外，DTIC@ HMLBF与DTIC@HMSNs和游离DTIC相比，对黑色素瘤细胞表现出最强的细胞毒性。体内研究表明，合理设计的负载DTIC的纳米载体通过靶向黑色素瘤细胞和肿瘤相关的巨噬细胞而实现对黑色素瘤肺转移的显著改善。该研究为设计和制备多功能纳米药物提供了一个很有前途的平台，这些药物可能用于治疗黑色素瘤。
Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability; and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying. HMSNs with carboxyl groups to enhance the loadingd of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release. In vitro, DTIC@HMLBFs exhibited the strongest cytotoxicity to melanoma cells compared with DTIC@HMSNs and free DTIC. The in vivo investigations demonstrate that the rationally designed nanocarrier loaded with DTIC achieves significant improvement against lung metastasis of melanoma via targeting melanoma cells and tumor-associated' macrophages. This study provides a promising platform for the design and fabrication of multifunctional nanomedicines, which are potentially useful for the treatment of melanoma.