MR Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
Sci Rep. 2020 Jun 26;10(1):10411. doi: 10.1038/s41598-020-67277-y.
As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.
作为一种天然多糖聚合物，糖原具有作为癌症治疗学中纳米颗粒载体的合适特性。它不仅具有固有生物相容性，还可以通过各种基团轻松进行化学修饰。由于肿瘤血管通透性增强和有限的淋巴引流（EPR 效应），合成的糖原缀合物可以被动地在肿瘤中积累。在这项研究中，我们开发并检查了一种含有镧系螯合物和近红外荧光染料的基于糖原的载体。我们的目的是使用磁共振和荧光成像监测荷瘤大鼠的生物分布和积累。我们的数据清楚地表明，这些缀合物具有合适的成像和肿瘤靶向特性，并且在体外和体内条件下都是安全的。用聚（2-烷基-2-恶唑啉）进一步修饰糖原聚合物，可降低其消除率并降低其在内脏器官中的摄取量（降低全身背景：与未修饰的相比，基于恶唑啉的缀合物在肝脏和肾脏中的 MRI 信号分别低 45%和 27%）。我们的结果强调了多模式基于糖原的纳米聚合物作为药物传递系统载体在肿瘤诊断和治疗中的潜力。
