Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier.
Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier.
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DOI：
10.1158/0008-5472.can-09-1157
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发表时间：
2009-08-01
期刊：
影响因子：
11.2
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Veiseh O;Sun C;Fang C;Bhattarai N;Gunn J;Kievit F;Du K;Pullar B;Lee D;Ellenbogen RG;Olson J;Zhang M
基于纳米颗粒的平台因其对肿瘤学和其他生物医学领域的潜在影响而引起了相当大的关注。然而，由于对靶标的特异性有限，它们的体内应用受到肿瘤内积累和保留不足的挑战，并且不能穿过生物屏障。在这里，我们提出了一种纳米探针，证明了在基因工程小鼠模型中穿过血脑屏障并特异性靶向脑肿瘤的能力，如通过体内MR和生物光子成像以及组织学和生物分布分析所建立的。该纳米探针由涂有生物相容性聚乙二醇接枝壳聚糖的氧化铁纳米颗粒组成，其上偶联有肿瘤靶向剂、氯毒素和近红外荧光团。纳米探针显示出无毒的毒性特征和在肿瘤中的持续保留。由于靶向配体的通用亲和力和用于替代诊断和治疗剂的灵活缀合化学，这种纳米颗粒平台可潜在地用于诊断和治疗各种肿瘤类型。
Nanoparticle-based platforms have drawn considerable attention for their potential impact on oncology and other biomedical fields. However, their in vivo application is challenged by insufficient accumulation and retention within tumors due to limited specificity to the target, and an inability to traverse biological barriers. Here we present a nanoprobe that demonstrates an ability to cross the blood-brain barrier and specifically target brain tumors in a genetically engineered mouse model, as established through in vivo MR and biophotonic imaging, and histological and biodistribution analyses. The nanoprobe is comprised of an iron oxide nanoparticle coated with biocompatible PEG-grafted chitosan, to which a tumor targeting agent, chlorotoxin and a near infrared fluorophore are conjugated. The nanoprobe demonstrates an innocuous toxicity profile and sustained retention in tumors. With the versatile affinity of the targeting ligand and the flexible conjugation chemistry for alternative diagnostic and therapeutic agents, this nanoparticle platform can be potentially used for diagnosis and treatment of a variety of tumor types.