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.
authors.affiliation: Department of Radiology, Sloan-Kettering Institute for Cancer Research,New York, New York 10065, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Benezra
authors.forename: Oula
authors.initials: O
authors.lastname: Penate-Medina
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: David
authors.initials: D
authors.lastname: Schaer
authors.forename: Hooisweng
authors.initials: H
authors.lastname: Ow
authors.forename: Andrew
authors.initials: A
authors.lastname: Burns
authors.forename: Elisa
authors.initials: E
authors.lastname: DeStanchina
authors.forename: Valerie
authors.initials: V
authors.lastname: Longo
authors.forename: Erik
authors.initials: E
authors.lastname: Herz
authors.forename: Srikant
authors.initials: S
authors.lastname: Iyer
authors.forename: Jedd
authors.initials: J
authors.lastname: Wolchok
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wiesner
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Bradbury
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D012822:Silicon Dioxide / Q000737:chemistry*; D013194:Staining and Labeling / Q000379:methods; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D004337:Drug Carriers; D007457:Iodine Radioisotopes; D008024:Ligands; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D012822:Silicon Dioxide