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生物素化 MnO 纳米立方体制备盐酸吉西他滨靶向递药系统及 MRI 应用

Biotinylated MnO nanocuboids for targeted delivery of gemcitabine hydrochloride to breast cancer and MRI applications.

机构信息

School of Nano Sciences, Central University of Gujarat, Gandhinagar 382030, India.

School of Life Sciences, Central University of Gujarat, Gandhinagar 382030, India.

出版信息

Int J Pharm. 2021 Sep 5;606:120895. doi: 10.1016/j.ijpharm.2021.120895. Epub 2021 Jul 17.

DOI:10.1016/j.ijpharm.2021.120895
PMID:34280487
Abstract

Multifunctional nanocarriers have been found as potential candidate for the targeted drug delivery and imaging applications. Herein, we have developed a biocompatible and pH-responsive manganese oxide nanocuboid system, surface modified with poly (ethylene glycol) bis(amine) and functionalized with biotin (Biotin-PEG-MNCs), for an efficient and targeted delivery of an anticancer drug (gemcitabine, GEM) to the human breast cancer cells. GEM-loaded Biotin-PEG@MNCs showed high drug loading efficiency, controlled release of GEM and excellent storage stability in the physiological buffers and different temperature conditions. GEM-loaded Biotin-PEG@MNCs showed dose- and time-dependent decrease in the viability of human breast cancer cells. Further, it exhibited significantly higher cell growth inhibition than pure GEM which suggested that Biotin-PEG@MNCs has efficiently delivered the GEM into cancerous cells. The role of biotin in the uptake was proved by the competitive binding-based cellular uptake study. A significant decrease in the amount of manganese was observed in biotin pre-treated cancer cells as compared to biotin untreated cancer cells. In MRI studies, Biotin-PEG-MNCs showed both longitudinal and transverse relaxivity about 0.091 and 7.66 mM s at 3.0 T MRI scanner, respectively. Overall, the developed Biotin-PEG-MNCs presents a significant potential in formulation development for cancer treatment via targeted drug delivery and enhanced MRI contrast imaging properties.

摘要

多功能纳米载体已被发现是靶向药物递送和成像应用的潜在候选物。在此,我们开发了一种具有生物相容性和 pH 响应性的氧化锰纳米立方体制备系统,其表面修饰有聚乙二醇双(胺)并用生物素(Biotin-PEG-MNCs)功能化,用于将抗癌药物(吉西他滨,GEM)高效靶向递送至人乳腺癌细胞。载有 GEM 的 Biotin-PEG@MNCs 具有高载药效率、GEM 的控制释放以及在生理缓冲液和不同温度条件下的优异储存稳定性。载有 GEM 的 Biotin-PEG@MNCs 表现出剂量和时间依赖性降低人乳腺癌细胞活力。此外,与纯 GEM 相比,它表现出显著更高的细胞生长抑制率,这表明 Biotin-PEG@MNCs 已将 GEM 有效递送至癌细胞内。通过基于竞争结合的细胞摄取研究证明了生物素在摄取中的作用。与未用生物素处理的癌细胞相比,在用生物素预处理的癌细胞中观察到锰的量显著减少。在 MRI 研究中,Biotin-PEG-MNCs 在 3.0 T MRI 扫描仪上分别表现出约 0.091 和 7.66 mM s 的纵向和横向弛豫率。总之,开发的 Biotin-PEG-MNCs 在通过靶向药物递送和增强 MRI 对比成像特性进行癌症治疗的制剂开发方面具有重要的潜在应用价值。

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