Abstract
Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles (SPIO) was prepared for drug delivery and magnetic resonance imaging (MRI). Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L−1. Doxorubicin (DOX) and a cluster of the manganese-doped iron oxide nanoparticles (Mn-SPIO) nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplatform for the delivery of anticancer drug DOX with a loading content (DLC) of 16 %. Confocal laser scanning microscopy reveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with free DOX·HCl. Under a 3.0-T MRI scanner, Mn-SPIO/DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation (T 2) rate is also significantly higher than that of the control cells (33.9 versus 2.3 s−1). Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.
摘要
多功能纳米颗粒能同时结合诊断和治疗试剂,有望实现肿瘤诊疗的一体化。本文制备了基于葡聚糖和超顺磁氧化铁纳米颗粒的多功能纳米复合物DOX/Mn-SPIO,用于药物传递和磁共振成像(MRI)。通过接枝硬脂酸到糖单元骨架上,获得临界胶束浓度为1.8 mg L−1的两亲性葡聚糖。经自组装的葡聚糖胶束可在疏水核负载抗肿瘤药物阿霉素和超顺磁氧化锰铁纳米晶体,形成粒径约100 nm的纳米复合物。体外细胞实验表明,该DOX/Mn-SPIO纳米复合物能作为有效传递抗肿瘤药物阿霉素的多功能纳米载体。相比游离的阿霉素药物,激光共聚焦显微镜结果表明该复合物在标记2 h时可高效进入人乳腺癌耐药细胞MCF-7/Adr。使用临床3 T磁共振扫描仪成像,该复合物标记的细胞MRI图像与对照组显示出明显对比度。其T 2弛豫率达33.9 s−1,显著高于对照组的2.3 s−1。研究表明该葡聚糖纳米胶束复合物作为诊疗一体化载体能在低剂量治疗MCF-7/Adr细胞的同时进行MRI成像,为MCF-7/Adr肿瘤细胞的诊疗提供了一种有效方法。
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Acknowledgments
This work was supported by the National Basic Research Program of China (2013CB933903), the National Key Technology Research and Development Program (2012BAI23B08), the National Natural Science Foundation of China (51173117), and the Scientific Research Start-up Fund of Kunming University of Science and Technology (KKSY201305089).
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The authors declare that they have no conflict of interest.
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Bingbing Lin and Hongying Su contributed equally to this work.
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Lin, B., Su, H., Jin, R. et al. Multifunctional dextran micelles as drug delivery carriers and magnetic resonance imaging probes. Sci. Bull. 60, 1272–1280 (2015). https://doi.org/10.1007/s11434-015-0840-x
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DOI: https://doi.org/10.1007/s11434-015-0840-x