Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy.
Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy.
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DOI：
10.1038/ncomms11221
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发表时间：
2016-04-13
影响因子：
16.6
通讯作者：
Mulder WJ
中科院分区：
文献类型：
--
作者：
Zhao Y;Fay F;Hak S;Manuel Perez-Aguilar J;Sanchez-Gaytan BL;Goode B;Duivenvoorden R;de Lange Davies C;Bjørkøy A;Weinstein H;Fayad ZA;Pérez-Medina C;Mulder WJ
癌症纳米治疗的一个主要目标是使用纳米颗粒作为载体，用于靶向递送抗肿瘤药物。静脉内给药后的药物-载体缔合对于向肿瘤有效递送药物是必不可少的。然而，大量目前可用的纳米载体是自组装的纳米颗粒，其载药稳定性受到体内环境的严重影响。在这里，我们使用体内FRET成像系统地研究药物载体相容性如何影响肿瘤小鼠模型中的药物释放。我们发现药物的疏水性和与纳米颗粒的相容性是决定其在肿瘤中积累的两个独立的关键参数。接下来，我们将这些发现应用于通过增强母体药物的相容性来改善化疗药物的递送;结果，我们获得了更好的抗肿瘤疗效。我们的研究结果有助于阐明纳米药物在体内的命运，并为有效的药物输送提供指导。 纳米粒子介导的药物递送的体内抗癌功效取决于药物与其载体之间的缔合。在这里，作者使用FRET来显示药物的疏水性和与载体的相容性影响小鼠肿瘤模型中的纳米颗粒积累。
A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug–carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug–carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery. The in vivo anticancer efficacy of nanoparticle-mediated drug delivery depends on the association between the drug and its carrier. Here, the authors use FRET to show that the drug hydrophobicity, and miscibility with the carrier, influence nanoparticle accumulation in murine tumour models.