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 α v β 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.

Gold–silica quantum rattles for multimodal imaging and therapy

“…Notwithstanding, the QRs are expected to perform in line with bare silica NP-based therapeutic/diagnostic systems both in terms of biodistribution and therapeutic effect (41). As silica particles, the QRs are easily amenable to biofunctionalization that can improve both their biodistribution and their therapeutic efficacy to clinically relevant degrees (44).…”

Biodegradable and Renal Clearable Inorganic Nanoparticles

“…These ultra‐small dense silica nanostructures are modified with near NIR dyes, cRGD, and radioisotopes, allowing for multimodality targeted imaging of cancer ( Figure 4 a) 4. With HD sizes of 6–8 nm, C dots have sufficiently long in vivo blood circulation time (t 1/2 = 190 min) to allow for optical imaging to be feasible throughout an entire surgery procedure 49.…”

“…Specifically, several inorganic platforms have been created that demonstrate potential in both preclinical and clinical trials 4, 5, 6, 7, 8, 9, 10, 11. Due to fast and high uptake in the reticuloendothelial system (RES; e.g.…”

Polymeric nanoparticles for optical sensing

“…Several reviews describing surface modifications of QDs for in vivo applications have been published recently (Dey et al, 2009;Sperling and Parak, 2010;Xing et al, 2009). Considering their biocompatibility, SNPs have been also employed as carriers for NIR dyes for in vivo imaging of mouse bladder (Burns et al, 2009), and for specific tumor imaging (Benezra et al, 2011). The main factors which affect the acute toxicity of SNPs include shape, porosity and their surface characteristics (Nakamura et al, 2007, Yu et al, 2012.…”