Detecting lenticulostriate artery lesions in patients with acute ischemic stroke using high-resolution MRA at 7 T.

BACKGROUND: Recent advances in high-resolution (HR) magnetic resonance angiography (MRA) using ultrahigh-field systems enable direct visualization of the lenticulostriate arteries (LSAs), which had been hardly achieved by conventional MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in the LSAs in patients with LSA territorial infarcts. METHODS: We prospectively examined 34 consecutive patients with acute ischemic stroke in the LSA territory using a 7 T scanner. We measured the lengths of the relevant LSAs on HR-MRA and the diameters/volume of the infarcts and compared these between the patients with/without occlusive changes in the LSAs. RESULTS: On HR-MRA, occlusion of the LSAs was observed in 19 (59%) of 32 patients who were eligible for the analyses. The curved/straight lengths of the LSAs in the patients with LSA occlusion (23.1-31.1/17.8-24.3 mm) were significantly shorter than in those without apparent LSA occlusion (25.8-39.5/24.0-30.4 mm) ( P = 0.027/0.003). The anteroposterior/superoinferior diameters of the infarcts were significantly larger in the occluded-LSA group (14.5-21.4/14.9-22.2 mm) than in the intact-LSA group (10.9-16.8/10.8-16.2 mm) ( P = 0.041/0.011). In addition, the curved lengths of the relevant LSAs showed significant correlations with the superoinferior diameters of the infarcts ( r = 0.38, P = 0.034). CONCLUSION: Occlusive changes in the LSAs were frequently found in patients with acute ischemic stroke within the LSA territory when using HR-MRA at 7 T and were substantially related to superoinferior extension of the infarcts.

Evaluation of Intraplaque Neovascularization Using Superb Microvascular Imaging and Contrast-Enhanced Ultrasonography.

BACKGROUND: Several studies have shown a linkage between intraplaque neovascularization (IPN) and plaque instability. Although contrast-enhanced ultrasonography (CEUS) may help visualize IPN in the carotid artery, its benefits are limited in Japan, where there is no health insurance coverage for contrast agents in medical imaging. Superb microvascular imaging (SMI), however, enables the depiction of low-velocity blood flow. The current study compares the diagnostic accuracy of SMI and CEUS in the evaluation of IPN. METHODS: The SMI and CEUS video images were transferred to a workstation and then analyzed to determine whether intraplaque blood flow signals were detected with SMI and whether plaques were contrast-enhanced with carotid artery CEUS. The images generated were independently interpreted by 2 radiologic technologists and 1 neurologist. RESULTS: Intraplaque enhancement was observed in 19 patients using CEUS while intraplaque blood flow signals were observed in 12 patients using SMI. A 100% specificity was recorded for SMI (all 12 patients with SMI-detected intraplaque blood flow showed contrast-enhanced plaques), while its sensitivity was 63% (8 of the 15 patients with no SMI-detected intraplaque blood flow showed contrast-enhanced plaques on CEUS). CONCLUSIONS: The results of this study show that patients with SMI-detected blood flow will tend to have plaque enhancement using CEUS. This suggests that SMI, as a simpler, safer, and noninvasive technique, can facilitate the visualization of carotid artery IPN without the use of a contrast agent, as well as in the clinical evaluation of plaque instability.

Intracranial Plaque Characterization in Patients with Acute Ischemic Stroke Using Pre- and Post-Contrast Three-Dimensional Magnetic Resonance Vessel Wall Imaging.

BACKGROUND: Magnetic resonance vessel wall imaging (VWI) techniques have been developed to assess atherosclerotic plaques in intracranial arteries, which are a cardinal cause of ischemic stroke. However, the clinical roles of plaque-related vulnerability and inflammation remain unclear. Hence, we evaluated plaque characteristics using VWI of the proximal middle cerebral artery (M1) in patients with acute ischemic stroke. METHODS: We prospectively examined 30 consecutive patients with acute noncardioembolic stroke in the M1 territory using pre-/postcontrast T1-weighted (T1W) three-dimensional (3D) VWI with a 3-Tesla scanner. The contrast ratio (CR) and contrast enhancement of the plaques were measured bilaterally at M1. RESULTS: Plaques were identified in the bilateral M1s of all patients, and no substantial stenosis existed. The M1 plaque CRs ipsilateral to the infarct (46.7%-67.9%) were significantly higher than the plaque CRs on the contralateral side (34.3%-69.4%), particularly in patients with lacunar infarcts (P <.01). In contrast, the occurrence of plaque enhancement was not different between the ipsilateral (20.0%) and contralateral (16.7%) sides. Further, the CRs in the nonlacunar group were significantly higher than the CRs in the lacunar group (P <.05), whereas enhanced plaques tended to be more frequent in the nonlacunar group, but this difference was not significant (P = .09). CONCLUSIONS: T1W 3D-VWI revealed that the signal intensity of M1 plaques was significantly higher in the affected side and in nonlacunar-type infarcts of patients with acute stroke, suggesting that unstable plaques in the M1 can cause stroke events presumably due to atherothrombotic mechanisms.

Carotid plaque characteristics on magnetic resonance plaque imaging following long-term cilostazol therapy.

BACKGROUND: Cilostazol is an antiplatelet agent that can induce the regression of atherosclerosis. However, its long-term effects on plaque involution of the cervical carotid arteries remain unknown. Thus, we aimed to evaluate the effect of long-term cilostazol administration on carotid plaques using quantitative magnetic resonance (MR) plaque imaging. METHODS: Sixteen consecutive patients with carotid stenosis were examined using T1-weighted MR plaque imaging at baseline, 6 months, and 12 months after initiation of 200 mg per day of cilostazol. We calculated the contrast ratio of the carotid plaque against the sternocleidomastoid muscle and percent areas of the intraplaque fibrous tissue, lipid/necrosis, and hemorrhage components using automated software. We also measured the volume and echogenicity of the plaques using 3-dimensional ultrasonography. RESULTS: The contrast ratio of the carotid plaque significantly decreased during the cilostazol administration (median 1.07, 1.04, and 1.00 at baseline, 6 months, and 12 months, respectively; P = .03). Furthermore, the area of the fibrous components significantly increased (73.9%, 80.3%, and 85.7%, respectively; P = .03) and that of the lipid/necrotic components significantly decreased (25.2%, 19.2%, and 14.3%, respectively; P = .04). There were no substantial changes in plaque volume or echogenicity on ultrasonography. CONCLUSIONS: Signal alterations on MR plaque imaging indicated the increase of fibrous components and the decrease of lipid/necrotic components in the carotid plaque during the cilostazol therapy.

Detection of vessel wall lesions in spontaneous symptomatic vertebrobasilar artery dissection using T1-weighted 3-dimensional imaging.

BACKGROUND: Spontaneous intracranial vertebrobasilar artery dissection (iVBD) is a cause of ischemic stroke and subarachnoid hemorrhage in young adults that can be detected noninvasively by using multisequence magnetic resonance imaging (MRI). However, MRI findings are sometimes difficult to interpret, and its accuracy tends to be suboptimal, especially during the acute period. Therefore, we investigated whether 3-dimensional (3D) vessel wall imaging (VWI) technique could readily detect iVBD lesions in acute phase patients. METHODS: Sixteen consecutive patients with acute ischemic stroke caused by iVBD were prospectively examined with a 1.5-T magnetic resonance scanner. T1-weighted (T1W) 3D-VWI was obtained using a flow-sensitized 3D fast spin-echo technique. In addition, multisequence MRI comprising magnetic resonance angiography (MRA), basiparallel anatomical scanning (BPAS), and axial T1W imaging (T1WI) were also examined. Presence of luminal stenosis, aneurysmal dilatation, intramural high signal, and intimal flap/double lumen of the vertebral and basilar arteries were visually assessed using each technique. RESULTS: On 3D-VWI, luminal stenosis, aneurysmal dilatation, intramural high signal, and intimal flap were observed in 16 (100%), 11 (68.8%), 16 (100%), and 1 (6.3%) patients, respectively. In contrast, on conventional techniques, these findings were observed in 15 (93.8%, MRA with BPAS), 12 (75.0%, MRA with BPAS), 12 (75.0%, T1WI), and 12 (75.0%, MRA) patients, respectively. CONCLUSIONS: The T1W 3D-VWI can directly visualize vessel wall iVBD lesions during the acute period of stroke compared with multisequence MRI.

D-glucosamine conjugation accelerates the labeling efficiency of quantum dots in osteoblastic cells.

Quantum dots (QDs) are useful imaging tools in the medical and biological fields due to their optical properties, such as a high fluorescence intensity, remarkable resistance to photobleaching, broad absorption spectra, and narrow emission spectra. This is the first study to investigate the uptake of carboxylated QDs conjugated with D-glucosamine (core size: approximately 3 nm, final modified size: 20-30 nm) into cultured osteoblastic cells. The QDs attached to the cell surface and were transported into the cytoplasm within approximately three hours of culture, whose process was clearly demonstrated using specific fluorescent staining of the cell membrane. Although the intranuclear distribution was not observed, a dramatic decrease in the transfer of quantum dots into the cytoplasm was recognized after approximately seven days of culture. Other interesting phenomena include the escape of the quantum dots from lysosomes in the cytoplasm, as confirmed by the merging of both QD fluorescence and specific fluorescent staining of lysosomes in the cytoplasm. These findings suggest that D-glucosamine conjugation enhances proton absorption in acid organelles and promotes the lysosomal escape of QDs.

Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging.

BACKGROUND: Atherosclerotic lesions in intracranial arteries are a leading cause of ischemic stroke. Magnetic resonance angiography (MRA) is often used to assess atherosclerotic changes by detecting luminal narrowing, whereas it cannot directly visualize atherosclerotic lesions. Here, we used a 3-dimensional vessel wall imaging (3D-VWI) technique to evaluate intracranial arterial wall changes in acute stroke. METHODS: Eighteen consecutive patients with acute noncardioembolic stroke in the middle cerebral artery (MCA) territory who were prospectively examined with a 1.5-T magnetic resonance scanner were studied. T1-weighted (T1-W) 3D-VWI was obtained using a flow-sensitized 3D fast-spin echo technique. Wall thickening of MCA that suggests atherosclerotic plaques was visually evaluated and the contrast ratio (CR) of signal intensity of the lesions to that of the corpus callosum was calculated and compared with stenotic changes by MRA. RESULTS: Wall thickenings of the MCA ipsilateral and contralateral to the lesion were observed in almost all patients on 3D-VWI (94.4% and 94.4%, respectively), whereas MRA showed stenotic changes of 50% only in 1 patient (5.9%; P < .001). The CR of the thickened wall in the ipsilateral MCA was significantly higher than that in the contralateral MCA (median, .53 and .45, respectively; P = .028), suggesting of unstable plaques consisting of hemorrhage or lipid. CONCLUSIONS: The T1-W 3D-VWI can provide direct visualization of atherosclerotic lesions of the intracranial arteries in stroke patients, and it can detect signal change suggestive of unstable plaque.

Carotid plaque signal differences among four kinds of T1-weighted magnetic resonance imaging techniques: a histopathological correlation study.

INTRODUCTION: Several magnetic resonance (MR) imaging techniques are used to examine atherosclerotic plaque of carotid arteries; however, the best technique for visualizing intraplaque characteristics has yet to be determined. Here, we directly compared four kinds of T1-weighted (T1W) imaging techniques with pathological findings in patients with carotid stenosis. METHODS: A total of 31 patients who were candidates for carotid endarterectomy were prospectively examined using a 1.5-T MRI scanner, which produced four kinds of T1W images, including non-gated spin echo (SE), cardiac-gated black-blood (BB) fast-SE (FSE), magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and source image of three-dimensional time-of-flight MR angiography (SI-MRA). The signal intensity of the carotid plaque was manually measured, and the contrast ratio (CR) against the adjacent muscle was calculated. CRs from the four imaging techniques were compared to each other and correlated with histopathological specimens. RESULTS: CRs of the carotid plaques mainly containing fibrous tissue, lipid/necrosis, and hemorrhage were significantly different with little overlaps (range: 0.92-1.15, 1.22-1.52, and 1.55-2.30, respectively) on non-gated SE. However, BB-FSE showed remarkable overlaps among the three groups (0.89-1.10, 1.07-1.23, and 1.01-1.42, respectively). MPRAGE could discriminate fibrous plaques from hemorrhagic plaques but not from lipid/necrosis-rich plaques: (0.77-1.07, 1.45-2.43, and 0.85-1.42, respectively). SI-MRA showed the same tendencies (1.01-1.39, 1.45-2.57, and 1.12-1.39, respectively). CONCLUSION: Among T1W MR imaging techniques, non-gated SE images can more accurately characterize intraplaque components in patients who underwent CEA when compared with cardiac-gated BB-FSE, MPRAGE, and SI-MRA images.

Quantitative assessment of changes in carotid plaques during cilostazol administration using three-dimensional ultrasonography and non-gated magnetic resonance plaque imaging.

INTRODUCTION: Cilostazol, an antiplatelet agent, is reported to induce the regression of atherosclerotic changes. However, its effects on carotid plaques are unknown. Hence, we quantitatively investigated the changes that occur within carotid plaques during cilostazol administration using three-dimensional (3D) ultrasonography (US) and non-gated magnetic resonance (MR) plaque imaging. METHODS: We prospectively examined 16 consecutive patients with carotid stenosis. 3D-US and T1-weighted MR plaque imaging were performed at baseline and 6 months after initiating cilostazol therapy (200 mg/day). We measured the volume and grayscale median (GSM) of the plaques from 3D-US data. We also calculated the contrast ratio (CR) of the carotid plaque against the adjacent muscle and areas of the intraplaque components: fibrous tissue, lipid, and hemorrhage components. RESULTS: The plaque volume on US decreased significantly (median at baseline and 6 months, 0.23 and 0.21 cm(3), respectively; p = 0.03). In the group exhibiting a plaque volume reduction of more than 10%, GSM on US increased significantly (24.8 and 71.5, respectively; p = 0.04) and CR on MRI decreased significantly (1.13 and 1.04, respectively; p = 0.02). In this group, in addition, the percent area of the fibrous component on MRI increased significantly (68.6% and 79.4%, respectively; p = 0.02), while those of the lipid and hemorrhagic components decreased (24.9% and 20.5%, respectively; p = 0.12) (1.0% and 0.0%, respectively; p = 0.04). There were no substantial changes in intraplaque characteristics in either US or MRI in the other group. CONCLUSIONS: 3D-US and MR plaque imaging can quantitatively detect changes in the size and composition of carotid plaques during cilostazol therapy.

Altered carotid plaque signal among different repetition times on T1-weighted magnetic resonance plaque imaging with self-navigated radial-scan technique.

INTRODUCTION: Magnetic resonance (MR) plaque imaging for carotid arteries is usually performed by using an electrocardiograph (ECG)-gating technique to eliminate pulsation-related artifacts, which can affect the plaque signals because of varied repetition time (TR) among patients. Hence, we investigated whether differences in TR causes signal alterations of the carotid plaque by using a non-gated plaque imaging technique. METHODS: We prospectively examined 19 patients with carotid stenosis by using a T1-weighted self-navigated radial-scan technique with TRs of 500, 700, and 900 ms. The signal intensity of the carotid plaque was measured, and the contrast ratio (CR) relative to the adjacent muscle was calculated. RESULTS: CRs of the carotid plaques were 1.39 +/- 0.39, 1.29 +/- 0.29, and 1.23 +/- 0.24 with TRs of 500, 700, and 900 ms, respectively, and were significantly different. Among the plaques, those with a hyperintensity signal (CR > 1.5) and moderate-intensity signal (CR 1.2-1.5) at 500 ms showed a TR-dependent signal decrease (hyperintensity plaques, 1.82 +/- 0.26; 1.61 +/- 0.19; and 1.48 +/- 0.17; moderate-intensity plaques, 1.33 +/- 0.08; 1.26 +/- 0.08; and 1.19 +/- 0.07), while those with an isointensity signal (CR < 1.2) remained unchanged regardless of TR (0.96 +/- 0.12, 0.96 +/- 0.11, and 0.97 +/- 0.13). CONCLUSION: The signal intensity of the carotid plaque on T1-weighted imaging significantly varies among different TRs and tends to decrease with longer TR. MR plaque imaging with short and constant TR settings that the ECG-gating method cannot realize would be preferable for evaluating plaque characteristics.

Immunostimulation-mediated antitumor activity by preconditioning with rice-shochu distillation residue against implanted tumor in mice.

We investigated the ability of rice-shochu postdistillation residue (RSDR) to stimulate the activity of macrophages. RSDR significantly stimulated mouse macrophage activity and induced significant IL-12 production in vitro. In syngeneic C38 solid tumor model in mice, a diet containing 1.0% RSDR caused a significant suppression of tumor growth and prolonged the life span of the tumor-bearing mice. Further, using this model, mice fed for 21 days with RSDR showed significantly increased levels of serum IL-12 and IFN-gamma compared with controls. Moreover, the splenic NK cell activity of mice fed with RSDR was significantly elevated compared with that of mice on a normal diet and thereby suppressed C38 tumor growth. We also investigated the tumor growth suppressing effect of RSDR using a tumor model of B16-F10 melanoma cells. Dietary preconditioning with RSDR significantly suppressed B16-F10 tumor growth. Moreover, RSDR significantly increased the production of IL-12 either before or after B16-F10 tumor implantation. These results suggest that dietary RSDR suppresses tumor growth by stimulating the immune system of the host.

Narrow CSF space at high convexity and high midline areas in idiopathic normal pressure hydrocephalus detected by axial and coronal MRI.

INTRODUCTION: The aim of this study was to determine the performance of axial and coronal magnetic resonance imaging (MRI) in detecting the narrowing of the cerebrospinal fluid (CSF) space at the high convexity and high midline areas, which is speculated to be one of the clinical characteristics of idiopathic normal pressure hydrocephalus (iNPH). METHODS: We retrospectively examined axial and coronal T1-weighted images of 14 iNPH patients and 12 age-matched controls. The narrowness of the CSF space at the high convexity/midline was blindly evaluated by five raters using a continuous confidence rating scale for receiver operating characteristic (ROC) analysis. RESULTS: Axial and coronal imaging accurately determined the presence of the narrow cisterns/sulci at the high convexity/midline and was capable of predicting probable/definite iNPH with a high degree of accuracy. there were also no significant differences in the detection of this finding between the axial and coronal images. CONCLUSION: Both axial and coronal T1-weighted MRI can detect the narrow CSF space at the high convexity/midline accurately and may therefore facilitate clinicians in choosing a management strategy for iNPH patients.

Chemically modified symmetric and asymmetric duplex RNAs: an enhanced stability to nuclease degradation and gene silencing effect.

The present study accents on the relationship between dicing, nuclease stability, and RNAi activity of various types of chemically modified symmetric and asymmetric dsRNAs, covalently bound with amino-groups or cholesterol at one or both terminals. All modified dsRNAs were subjected to cleavage by recombinant Dicer enzyme. They possessed a high resistance to nuclease degradation in cell cultured medium and an excellent RNAi activity in viable cells. The best stability and RNAi activity was detected for 5'-sense amino-modified RNAs. These modifications manifested also a high long-term gene silencing effect within seven days post-transfection, while the RNAi activity of the native 21nt siRNA expired within two days. The conjugation of dsRNA with cholesterol at 5'-sense end resulted in easy intracellular delivery without transfection reagents. After a direct transfection in cells, the cholesterol-conjugated 27nt dsRNA possessed a higher RNAi activity than cholesterol-conjugated 21nt siRNA.

Enhancement of gene silencing potency and nuclease stability by chemically modified duplex RNA.

In this study, we describe a development of chemically modified dsRNAs with improved biological properties. These dsRNAs possess an enhanced RNAi activity and a dramatically increased stability in cell cultured medium (containing 10% serum) in comparison with widely used 21nt siRNA. The chemically modified dsRNAs manifested a high longterm gene suppression after one week post-transfection, whereas 21nt siRNA showed a high RNAi activity only after 48 h cell transfection.

Synthesis of phosphorothioate oligonucleotide-peptide conjugates by solid phase fragment condensation.

Phosphorothioate oligonucleotide-peptide conjugates were synthesized by solid phase fragment condensation (SPFC). Arginine rich peptides could be successfully conjugated in 2.8-13.4% isolated yields. All the products were fully characterized by reversed phase HPLC and MALDI-TOF-MS to give satisfactory results.

Modified 27-nt dsRNAs with dramatically enhanced stability in serum and long-term RNAi activity.

The present study describes improved properties of 27-nt dsRNAs over 21-nt siRNAs, and accents on the possibility to use their modifications and conjugates for direct long-term gene silencing in viable cells and animals, avoiding conventional transfectants. Using a Renilla Luciferase gene-silencing system and cultured cell lines, we established that 27-nt dsRNAs possessed about three to five times higher "long-term" RNAi activity than 21-nt siRNAs and 21-nt dsRNAs. Moreover, if RNA duplexes were preincubated with cell-cultured medium for several hours before their transfection in cells, 21-mer completely lost its RNAi effect, while 27-mer, its amino modifications, thiol modifications, and cholesterol conjugates manifested a strong gene silencing. In attempts to clarify the reason(s) for the higher RNAi activity of 27-nt dsRNAs, we found that they were approximately 100 times more stable than 21-nt siRNA and 21-nt dsRNA in cell-cultured medium supplemented with 10% inactivated serum, approximately 50 times more stable in 90% inactivated serum, and approximately six times more stable in active serum. The 5' sense modification was selected as the most stable, accessible to Dicer, and with highest RNAi potential. The RNAi activity of 5' sense modifications was higher even than the activity of nonmodified 27-nt dsRNA. The 5' sense amino modification also did not influence the activity of 21-nt siRNA, right overhang 25/27-nt (R25D/27), and 25D/27-nt RNAs. The stability of 5' sense modified R25D/27-nt and 25D/27-nt RNAs in serum was lower than that of blunt 27-nt dsRNA. However, these asymmetric RNAs were more active than modified and nonmodified blunt 27-nt dsRNAs, which demonstrates the superiority of the asymmetric design. The 5' sense modifications were considered as most appropriate for conjugation with small signal molecules to facilitate the intracellular delivery of RNA duplex, to preserve its RNAi capacity, and to ensure a possibility for rapid long-term gene silencing in viable cells and animals. The 5' sense conjugation with cholesterol approved this assumption.

Dual-labeled telomere sensing probes for quantification of telomerase activity assay.

The present study describes an empirically discovered phenomenon that might be useful for development of a sensitive and rapid methodology for quantification of telomerase activity assay with simple data acquisition and possibility for calculation of telomerase product in absolute units. The method is based on the design and application of two single-stranded telomere sensing probes consisting of dual-labeled 16-mer oligonucleotides (fluorescent Cy3/Cy3-labeled and non-fluorescent IowaBlack/BHQ-labeled) that can simultaneously hybridize on the primary product of the telomerase reaction.

Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality.

The present study describes a stabilization of single quantum dot (QD) micelles by a "hydrophobic" silica precursor and an extension of a silica layer to form a silica shell around the micelle using "amphiphilic" and "hydrophilic" silica precursors. The obtained product consists of approximately 92% single nanocrystals (CdSe, CdSe/ZnS, or CdSe/ZnSe/ZnS QDs) into the silica micelles, coated with a silica shell. The thickness of the silica shell varies, starting from 3-4 nm. Increasing the shell thickness increases the photoluminescence characteristics of QDs in an aqueous solution. The silica-shelled single CdSe/ZnS QD micelles possess a comparatively high quantum yield in an aqueous solution, a controlled small size, sharp photoluminescence spectra (fwhm approximately 30 nm), an absence of aggregation, and a high transparency. The surface of the nanoparticles is amino-functionalized and ready for conjugation. A comparatively good biocompatibility is demonstrated. The nanoparticles show ability for intracellular delivery and are noncytotoxic during long-term incubation with viable cells in the absence of light exposure, which makes them appropriate for cell tracing and drug delivery. The presence of the hydrophobic layer between the QD and silica-shell ensures an incorporation of other hydrophobic molecules with interesting properties (e.g., hydrophobic paramagnetic substances, hydrophobic photosensitizers, membrane stabilizers, lipid-soluble antioxidants or prooxidants, other hydrophobic organic dyes, etc.) in the close proximity of the nanocrystal. Thus, it is possible to combine the characteristics of hybrid materials with the priority of small size. The silica-shelled single QD micelles are considered as a basis for fabrication of novel hybrid nanomaterials for industrial and life science applications, for example, nanobioprobes with dual modality for simultaneous application in different imaging techniques (e.g., fluorescent imaging and functional magnetic resonance imaging).

Single quantum dot-micelles coated with silica shell as potentially non-cytotoxic fluorescent cell tracers.

The present study describes a stabilization of single quantum dot (QD) micelles by hydrophobic silica precursors and an extension of the silica layer to form a silica shell around the micelle. The obtained product consists of up to 92% of single nanocrystals (CdSe, CdSe/ZnS, or CdSe/ZnSe/ZnS quantum dots) in the silica micelles, coated with silica shell. The thickness of silica shell could vary, starting from 3 to 4 nm. Increasing the shell thickness increases the photoluminescent characteristics of QDs in aqueous solution. The silica-shelled single CdSe/ZnS QD micelles possess a high quantum yield in aqueous solution, a controlled small size, sharp photoluminescence spectra (fwhm approximately 30 nm), an absence of aggregation, and a high transparency. The presence of a hydrophobic layer between the QD and silica shell ensures an incorporation of other hydrophobic molecules (with interesting properties) in the close proximity of nanocrystal. Thus, it is possible to combine the characteristics of hybrid material with the priority of small size. The nanoparticles are amino functionalized and ready for conjugation. A comparatively good biocompatibility is demonstrated. The nanoparticles show ability for intracellular delivery and are noncytotoxic during long-term incubation with viable cells in the absence of light exposure, which makes them appropriate for cell tracing and drug delivery.