Tumor-targeted drug delivery using MR-contrasted docetaxel - Carboxymethylcellulose nanoparticles

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• 作者：Mark J. Ernsting^a ; Warren D. Foltz^b ; Elijus Undzys^a ; Tatsuaki Tagami^a ; Shyh-Dar Li^a ; ^{sli@oicr.on.ca}
• 关键词：Docetaxel ; Carboxymethylcellulose ; Conjugated Polymers ; Magnetic nanoparticles
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：May, 2012
• 卷：33
• 期：15
• 页码：3931-3941
• 文件大小：3166 K

摘要

A carboxymethylcellulose-based polymer conjugate with nanoparticle forming properties (Cellax) has been shown to enhance the pharmacokinetics, specificity of biodistribution, anti-tumor efficacy and safety of docetaxel (DTX) in comparison to the Taxotere鈩?formulation. We examined Cellax and Taxotere efficacy in four tumor models (EMT-6, B16F10, PC3, and MDA-MB-231), and observed variances in efficacy. To explore whether differences in tumor uptake of Cellax were responsible for these effects, we incorporated superparamagnetic iron oxide nanoparticles (SPIONs) into Cellax particles to enable magnetic resonance (MR) imaging (Cellax-MR). In the EMT-6 tumor model, Cellax-MR nanoparticles exhibited peak tumor accumulation 3-24聽h post intravenous injection, and 3 days post-treatment, significant MR contrast was still detected. The amount of Cellax-MR deposited in the EMT-6 tumors was quantifiable as a hypointense volume fraction, a value positively correlated with drug content as determined by LC/MS analysis (R²聽=聽0.97). In the four tumor models, Cellax-MR uptake was linearly associated with anti-tumor efficacy (R²聽>聽0.9), and was correlated with blood vessel density (R²聽>聽0.9). We have affirmed that nanoparticle uptake is variable in tumor physiology, and that this efficacy-predictive parameter can be non-invasively estimated in real-time using a theranostic variant of Cellax.