Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 121, Issue 7, Pages 2768-2780Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI45600
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Funding
- NIH-American Recovery and Reinvestment Act/Clinical and Translational Science Center
- Cornell Nanobiotechnology Center
- National Science Foundation [ECS-9876771]
- In vivo Cellular and Molecular Imaging Center [P50 CA86438]
- NIH [R24 CA83084, P30 CA08748]
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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.
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