Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent
Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent
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DOI：
10.1021/acs.biomac.5b00867
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发表时间：
2015-09-01
影响因子：
6.2
通讯作者：
Almutairi, Adah
中科院分区：
文献类型：
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作者：
Chan, Minnie;Lux, Jacques;Almutairi, Adah
临床批准的小分子磁共振成像（MRI）造影剂都能迅速从体内清除，并提供微弱的信号增强。为了避免重复给予造影剂并提高信噪比，需要具有更强信号增强和更好保留在肿瘤中的药剂。因此，我们专注于水凝胶，因为它们具有出色的水可及性和生物降解性。钆（Gd）螯合交联剂被纳入自组装普鲁兰多糖纳米凝胶，既赋予磁性，并稳定这种材料，已被广泛研究的医疗应用。我们表明，这些Gd螯合普鲁兰多糖纳米凝胶（Gd-CHPOA）具有最高的报告弛豫率的任何水凝胶为基础的颗粒，并在4 T1小鼠肿瘤中积累在高水平注射后4小时。这种组合提供了高信号增强，并持续长达7天，以更长的成像时间尺度清楚地描绘肿瘤。重要的是，这种长期积累在注射后长达三个月不会对主要器官造成任何损害或毒性。我们的工作突出了Gd-CHPOA作为肿瘤成像MRI造影剂的临床潜力，允许肿瘤识别和评估具有高信号背景比。
Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd-CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio.