Benezra M, Penate-Medina O, Zanzonico PB et al.Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J Clin Invest 121:2768-2780

Department of Radiology, Sloan-Kettering Institute for Cancer Research,New York, New York 10065, USA.
The Journal of clinical investigation (Impact Factor: 13.22). 06/2011; 121(7):2768-80. DOI: 10.1172/JCI45600
Source: PubMed


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.

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    • "Indeed, the surface of silica nanoparticles can be modified with chemical functional groups like addition of specific antibodies or fluorescent labels for specific drug delivery (targeting of cancer cells) or specific diagnosis (tumor labeling )(Chandolu and Dass 2013). As an example, dyedoped fluorescent (Cyanine-5) silica nanoparticles (8 nm in diameter), known as ''Cornell dots,'' have been approved in 2011 by the US Food and Drug Administration (FDA) for human stage I molecular imaging of cancer (Benezra et al. 2011). Those confirm the importance of future clinical potentials of silica-based nanoparticles as effective and specific medical tools. "
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    ABSTRACT: Silica nanoparticles are particularly inter-esting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nano-particles were synthesized: (1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol molecules, (2) positively charged silica nano-particles coated with amine groups, and (3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 h with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay, and cellular responses were evaluated in terms of cytotox-icity, pro-inflammatory factor production, and oxida-tive stress. Results showed that the highly positively charged nanoparticle were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticle types. To conclude, this study clearly demonstrated that silica nanoparticles surface func-tionalization represents a key parameter in their cellular uptake and biological toxicity.
    Journal of Nanoparticle Research 11/2014; 16(11):2738. · 2.18 Impact Factor
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    • "In order to target M21 melanomas in a xenograft mouse model, multimodal SNPs were coated with bifunctional methoxy-terminated polyethylene glycol (PEG) chains ($0.5 kDa; 7 nm). Neutral charged PEG functionalized SNPs were poorly uptaken by noncancer cells, and the bifunctional group enabled attachment of the integrin targeting RGDY peptide labeled with 124 I (Benezra et al., 2011). In another study, functionalized mesoporous silica (FMS) with a rigid, uniform, open nanopore geometry of tens of nanometers was used for loading of a monoclonal antibody (mAb) binding to CTLA4-an immunoregulatory molecule overexpressed in melanoma (Leach et al., 1996). "
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    ABSTRACT: Abstract Nanotechnology is a rapidly expanding area of research involved in developing science-based solutions for innovative therapeutics. Silica nanoparticles (SNPs) have received wide attention in several industries and medicine and are being developed for biomedical and biotechnological applications such as drug delivery, DNA transfection, and targeted molecular imaging of cancer. Recently, they are emerging in the fields of cosmetics and dermal preparations. SNP may offer a revolutionized treatment of several skin diseases by controlled and sustained release of drugs to skin, as well as enhanced skin penetration of encapsulated drug ingredients. SNPs are candidates for transcutaneous vaccination and transdermal gene therapy, too. Yet there exist concerns that whilst the properties of SNPs have enabled numerous industrial and medical applications, their toxicological and environmental safety mandates evaluation. The knowledge of passage of SNPs through skin following skin exposure (intentionally or unintentionally) and subsequent effects is limited. This review surveys the key experiments on SNP-based formulations in the fields of dermatology and cosmetics with the goal of rationalizing data and informing public health concerns related to SNPs' toxicity among scientists and manufacturers handling them, while highlights the research gaps in dermal absorption of these compounds.
    Nanotoxicology 10/2014; 9(5):1-15. DOI:10.3109/17435390.2014.958115 · 6.41 Impact Factor
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    • "For example, cyanine dye-doped silica NPs were reported to directly discriminate live and early-stage apoptotic stem cells (both mesenchymal and embryonic) through a distinct external cell surface distribution,68 which makes them ideal for stem cell labeling and tracking.67 Recently, Cy5 encapsulated 7nm fluorescent silica NPs were functionalized with both cyclic RGD peptide and radioactive iodine for tumor imaging in a mouse model of melanoma.69 (Figure 5A) This ultra-small multimodal silica NPs exhibited high-affinity binding, favorable tumor-to-blood residence time ratios, and excellent tumor-selectivity on αvβ3 integrin-expressing melanoma xenografts in mice. "
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    ABSTRACT: Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat. To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood. To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells. Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking. Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research. Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products.
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