Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma Journal Article
| Authors: | Benezra, M.; Penate-Medina, O.; Zanzonico, P. B.; Schaer, D.; Ow, H.; Burns, A.; Destanchina, E.; Longo, V.; Herz, E.; Iyer, S. ; Wolchok, J.; Larson, S. M.; Wiesner, U.; Bradbury, M. S. |
| Article Title: | Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma |
| Abstract: | 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 arginine-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 αvβ3 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. |
| Keywords: | controlled study; protein expression; human cell; nonhuman; positron emission tomography; lymph node metastasis; binding affinity; mouse; animal tissue; melanoma; computer assisted tomography; animal experiment; animal model; tumor xenograft; cancer model; axillary lymph node; radioactive iodine; dosimetry; radioactivity; fluorodeoxyglucose f 18; ligand; radiopharmaceutical agent; kidney clearance; nanoparticle; silicon dioxide; iodine 124; dye; inguinal lymph node; lymphatic drainage; molecular probe; arginylglycylaspartic acid; quantum dot; drug excretion; lymphatic system examination; particle size; receptor binding; fluorescence imaging; lymph node mapping; whole body pet; molecularly targeted therapy; vitronectin receptor; nanoencapsulation; minipig |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 121 |
| Issue: | 7 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2011-07-01 |
| Start Page: | 2768 |
| End Page: | 2780 |
| Language: | English |
| DOI: | 10.1172/jci45600 |
| PROVIDER: | scopus |
| PUBMED: | 21670497 |
| PMCID: | PMC3223837 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: JCINA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work