Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma
Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma
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DOI：
10.1172/jci45600
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发表时间：
2011-07-01
影响因子：
15.9
通讯作者：
Bradbury, Michelle S.
中科院分区：
文献类型：
--
作者：
Benezra, Miriam;Penate-Medina, Oula;Bradbury, Michelle S.
基于纳米颗粒的材料，如药物输送载体和诊断探针，目前正在肿瘤临床试验中进行评估，很大程度上不具有肿瘤选择性。为了在临床上取得成功，下一代纳米颗粒药物应该具有肿瘤选择性，无毒，并具有良好的靶向性和清除率。开发符合这些标准的探针具有挑战性，需要全面的体内评估。在这里，我们描述了我们对直径约7纳米的多模态二氧化硅纳米颗粒的完整表征，展示了我们认为是结构，光学和生物特性的独特组合。这种超小的癌症选择性二氧化硅颗粒最近被批准用于首次人体临床试验。优化有效的肾脏清除，同时实现特异性肿瘤靶向。染料包埋颗粒表面被环精氨酸-甘氨酸-天冬氨酸肽配体和放射性碘功能化，在表达α (v) β(3)整合素的小鼠黑色素瘤异种移植物中表现出高亲和力/亲和力结合、有利的肿瘤-血液停留时间比和增强的肿瘤选择性积累。此外，在大型黑色素瘤动物模型中，淋巴引流模式、颗粒清除率、淋巴结转移和肿瘤差异负荷的敏感、实时检测和成像突出了这种多模式平台在临床环境中转移性疾病分期的独特潜在优势。
Nanoparticle-based materials, such as drug delivery vehicles and diagnostic probes, currently under evaluation in oncology clinical trials are largely not tumor selective. To be clinically successful, the next generation of nanoparticle agents should be tumor selective, nontoxic, and exhibit favorable targeting and clearance profiles. Developing probes meeting these criteria is challenging, requiring comprehensive in vivo evaluations. Here, we describe our full characterization of an approximately 7-nm diameter multimodal silica nanoparticle, exhibiting what we believe to be a unique combination of structural, optical, and biological properties. This ultrasmall cancer-selective silica particle was recently approved for a first-in-human clinical trial. Optimized for efficient renal clearance, it concurrently achieved specific tumor targeting. Dye-encapsulating particles, surface functionalized with cyclic argiruine-glycine-aspartic acid peptide ligands and radioiodine, exhibited high-affinity/avidity binding, favorable tumor-to-blood residence time ratios, and enhanced tumor-selective accumulation in alpha(v)beta(3) integrin-expressing melanoma xenografts in mice. Further, the sensitive, real-time detection and imaging of lymphatic drainage patterns, particle clearance rates, nodal metastases, and differential tumor burden in a large-animal model of melanoma highlighted the distinct potential advantage of this multimodal platform for staging metastatic disease in the clinical setting.