Specific Targeting, Cell Sorting, and Bioimaging with Smart Magnetic Silica Core–Shell Nanomaterials

Yoon, Tae‐Jong; Yu, Kyeong Nam; Kim, Eunha; Kim, Jun Sung; Kim, Byung Geol; Yun, † Sang-Hyun; Sohn, Byeong‐Hyeok; Cho, Myung‐Haing; Lee, Jin‐Kyu; Park, Seung Bum

doi:10.1002/smll.200500360

Cited by 291 publications

(191 citation statements)

References 58 publications

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“…Reactive derivatives of the organic dye Cy5, exhibiting emission maxima about 650 nm, were used to produce particles containing 2 dye equivalents within the particle core. Tyrosine residues were conjugated to PEG chains (48,49) for attachment of radioiodine or stable iodine moieties. All samples were optical density matched at their peak absorption wavelength (640 nm) prior to radiolabeling.…”

Section: Synthesis Of Crgdy-peg-dots Crady-peg-dots and Peg-dotsmentioning

confidence: 99%

Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma

Benezra¹,

Peñate-Medina²,

Zanzonico³

et al. 2011

J. Clin. Invest.

592

476

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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 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.

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Section: Synthesis Of Crgdy-peg-dots Crady-peg-dots and Peg-dotsmentioning

confidence: 99%

Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma

Benezra¹,

Peñate-Medina²,

Zanzonico³

et al. 2011

J. Clin. Invest.

592

476

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show abstract

“…Magnetic-core nanoparticles contain only cobalt ferrite without a silica coating. The basic core nanoparticles were commercially designed by Biterials, and the procedure for basic core synthesis was as previously described (5,15). Briefly, cobalt ferrite magnetics were stabilized using polyvinyl pyrrolidone (Sigma) solution.…”

Section: Methodsmentioning

confidence: 99%

Gene Expression Profiles for Genotoxic Effects of Silica-Free and Silica-Coated Cobalt Ferrite Nanoparticles

Hwang¹,

Lee²,

Kim³

2011

J Nucl Med

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Nanomaterials have been widely evaluated for potential use as efficient delivery carriers for cancer diagnosis and therapy. To translate these nanomaterials to the clinic, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. We investigated changes in gene expression profiles influenced by silica-coated cobalt ferrite magnetic-fluorescence nanoparticles and silica-free cobalt ferrite magnetic-core nanoparticles in vivo and in vitro. Methods: 68 Ga-labeled cobalt ferrite nanoparticles produced by synthesis of 2-(p-isothio-cyanatobenzyl)-1,4,7-triazacyclonane-1,4,7-triacetic acid chelator were established after labeling efficiency had been validated through a thin-layer chromatography method. The expression of genes associated with the stress and toxicity pathways was verified by a commercially available polymerase chain reaction array kit. Results: In comparison with magnetic-fluorescence nanoparticles, magnetic-core nanoparticles revealed severe cytotoxic effects at various doses and treatment times as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Whole-body small-animal PET and biodistribution studies, including transmission electron microscope analysis, showed that tail-vein injection of magneticcore or magnetic-fluorescence nanoparticles exhibited substantial liver accumulation. Real-time polymerase chain reaction array using 52 genes related to cellular toxicity demonstrated that 17 genes from the magnetic-core-treated liver samples were significantly affected, mostly in relation to DNA damage or repair and to oxidative or metabolic stress. The magnetic-fluorescence-treated liver samples showed gene expression approximately 90% similar to that of untreated liver samples. Conclusion: We compared a variety of gene expression profiles in mice injected with magnetic-fluorescence or magnetic-core nanoparticles. This study of gene expression profiles affected by nanotoxicity provides critical information for the clinical use of silica-coated cobalt ferrite.

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“…We have previously reported the synthesis of organic dyeincorporated MNP-SiO 2 (RITC), which exhibited increased fluorescence intensity and photostability. 15,16 In this study, we prepared NPs with various amounts of organic dye (2.08 mg, 4.17 mg, 8.35 mg, and 12.52 mg) to increase the fluorescent intensity and optimize the synthesis. After the successful preparation of fluorescent NPs, we measured their shape by TEM and their fluorescence intensity by fluorescent spectrometer.…”

Section: Characterization Of Mnp-sio 2 (Ritc) and Muc1-mnp-sio 2 (Ritc)mentioning

confidence: 99%

“…The size was maintained at 50 nm in order to maintain the water-solubility and dispersibility of MNP-SiO 2 (RITC), on the basis of previous studies (Figure 3). 15,16 As a result of optimization, we successfully increased the fluorescence intensity of MNP-SiO 2 (RITC) fourfold, with an optimized organic dye concentration of 8.35 mg.…”

mentioning

confidence: 99%

One-step detection of circulating tumor cells in ovarian cancer using enhanced fluorescent silica nanoparticles

Kim¹,

Chung²,

Jeong³

et al. 2013

IJN

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Ovarian cancer is the fifth-leading cause of cancer-related deaths among women as a result of late diagnosis. For survival rates to improve, more sensitive and specific methods for earlier detection of ovarian cancer are needed. This study presents the development of rapid and specific one-step circulating tumor cell (CTC) detection using flow cytometry in a whole-blood sample with fluorescent silica nanoparticles. We prepared magnetic nanoparticle (MNP)-SiO 2 (rhodamine B isothiocyanate [RITC]) (MNP-SiO 2 [RITC] incorporating organic dyes [RITC, λ max(ex/em) = 543/580 nm]) in the silica shell. We then controlled the amount of organic dye in the silica shell of MNP-SiO 2 (RITC) for increased fluorescence intensity to overcome the autofluorescence of whole blood and increase the sensitivity of CTC detection in whole blood. Next, we modified the surface function group of MNP-SiO 2 (RITC) from -OH to polyethylene glycol (PEG)/COOH and conjugated a mucin 1 cell surface-associated (MUC1) antibody on the surface of MNP-SiO 2 (RITC) for CTC detection. To study the specific targeting efficiency of MUC1-MNP-SiO 2 (RITC), we used immunocytochemistry with a MUC1-positive human ovarian cancer cell line and a negative human embryonic kidney cell line. This technology was capable of detecting 100 ovarian cancer cells in 50 µL of whole blood. In conclusion, we developed a one-step CTC detection technology in ovarian cancer based on multifunctional silica nanoparticles and the use of flow cytometry.

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Specific Targeting, Cell Sorting, and Bioimaging with Smart Magnetic Silica Core–Shell Nanomaterials

Cited by 291 publications

References 58 publications

Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma

Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma

Gene Expression Profiles for Genotoxic Effects of Silica-Free and Silica-Coated Cobalt Ferrite Nanoparticles

One-step detection of circulating tumor cells in ovarian cancer using enhanced fluorescent silica nanoparticles

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