Targeted Imaging Applications Research Articles

Synthesis, characterization, and in-vitro bioimaging applications of green emissive AgInS2-based core multi and alloyed shell (AgInS2/CdS/ZnS and AgInS2/ZnS/CdS) nanocrystals

This study explores the synthesis, characterization, and preliminary bioimaging applications of green-emissive AgInS2-based nanocrystals (NCs) featuring core-multi and alloyed shell structures, specifically AgInS2/CdS/ZnS and AgInS2/ZnS/CdS. The nanocrystals were synthesized using a controlled hot-injection method, which ensured the formation of uniform core–shell structures. Detailed characterization through X-ray diffraction (XRD), transmission electron microscopy (TEM), and photoluminescence spectroscopy confirmed the successful development of these core-multi and alloyed shell architectures. The photoluminescence quantum yields (QY) were determined to be approximately 25 % for AgInS2/CdS/ZnS and 30 % for AgInS2/ZnS/CdS, highlighting their efficient luminescent properties. In preliminary bioimaging studies, these nanocrystals exhibited effective cellular imaging capabilities. They showed pronounced fluorescence with minimal background interference in A549 and U87MG cells, suggesting their potential for precise and targeted imaging applications. Despite these promising results, further investigation is needed to fully understand the specificity of these nanocrystals and their interaction mechanisms with various cell types. The observed quantum yields and targeted imaging capabilities indicate that AgInS2-based nanocrystals are promising candidates for advanced bioimaging technologies.

Bioimaging based on Poly(ethylenimine)-Coated Carbon Dots and Gold Nanoparticles for pH Sensing and Metal Enhanced Fluorescence.

When exposed to specific light wavelengths, carbon dots (CDs), which tend to be fluorescent, can emit colorful light. It provides them with a lot of adaptability for different applications including bioimaging, optoelectronics, and even environmental sensing. Poly(ethylenimine) (PEI) coated carbon dots (PEI-CDs) with a long emission wavelength were synthesized via the hydrothermal method. The resultant CDs show strong fluorescence with quantum yield up to 20.2%. The PEI-CDs exist with distinct pH-sensitive features with pH values in the range of 2-14. The optical characteristics of CDs are pH-responsive due to the presence of different amine groups on PEI, which is a functional polycationic polymer. One of the most widely employed nanoparticles for improving the fluorescence plasmonic characteristics of a nanocomposite is gold. Gold nanoparticles were coupled with PEI-CDs in this assay by using the EDC-NHS coupling to increase the photoluminescence property of the PEI-CDs by using the metal-enhanced fluorescence approach. In the presence of gold nanoparticles, the fluorescence is enhanced 5-6 times. The likely mechanism in our investigation was primarily derived from enhancement of the intrinsic radiative decay rate rather than the local electric field impact. Moreover, PEI-CDs can be used as a bioimaging agent, as these molecules are nontoxic to the cells, and the positively charged PEI-CDs have the potential for nuclear targeting, allowing for electrostatic contact with DNA in the nucleus. This finding will expand the application that the PEI-CDs can be used in the future for targeted imaging applications.

Investigation of Gd2O3: Er3+/Yb3+ Upconversion Nanoparticles (UCNPs) as a Multi-model Contrast Agent for Functional Optical Coherence Tomography (fOCT).

Currently, upconversion nanoparticles (UCNPs) implanted as a contrast agent for optical coherence tomography (OCT) system due to its biocompatibility, anti-stock emission, narrow emission bandwidth non-photobleaching effects etc., but it was not used as multi model imaging probe. We synthesized multimodal imaging probe having upconversion property along with paramagnetic property and used as dual contrast agents for Photothermal Optical Coherence Tomography (PTOCT) and Magnetomotive Optical Coherence Tomography (MMOCT). The synthesized Gd2O3:Er3+/Yb3+ UCNPs shows the bright yellow upconversion emission, biocompatibility with hydrophilic property. A custom built SSOCT setup modified for PTOCT and MMOCT imaging along with custom MATLAB algorithm for signal extraction. A dynamic study was performed with synthesized UCNPs as an imaging probe and functional OCT system for targeted imaging. This shows the utility of the Gd2O3:Er3+/Yb3+ UCNPs as molecular probe for targeted imaging applications.

Correction: Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications.

Correction for 'Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications' by Lining Sun et al., Nanoscale, 2014, 6, 8878-8883.

Multifunctional Microbubbles in Ultrasound Theranostics

The discipline of medical imaging is expanding beyond an assessment of anatomical structure to functional imaging and an assessment of the nature and extent of disease. This advancement is made possible by recent discoveries in molecular science, which provide the opportunity to design targeted contrast agents. Targeted imaging using ultrasound relies on contrast agents to localize a specific molecular signature or physiologic system and combines the efficacy of a contrast agent with an adhesion molecule to target the contrast directly to the desired region. Current ultrasound contrast agents are encapsulated microbubbles and have demonstrated effectiveness in cardiology and radiology. These contrast agents become identifiers of a specific molecular signature either by their preferential uptake by a physiologic system or by specific targeting of the agent through incorporation of adhesion molecules into the microbubble shell. Targeted ultrasound contrast agents provide an opportunity to image physiology or pathology that might be otherwise difficult to distinguish from the surrounding tissue without targeted contrast enhancement. This talk proposes the multi-functional microbubbles employed with ultrasound for drugs delivery/release, mechanical cell destruction, and US/MRI targeted imaging applications, thus presenting a new strategy for ultrasound theranostics.

Developing Magnetic Particle Imaging (MPI) tracers for in vivo tissue-targeted applications

Event Abstract Back to Event Developing Magnetic Particle Imaging (MPI) tracers for in vivo tissue-targeted applications Hamed Arami1, Haydin Bradshaw1, Eric Teeman1, Alyssa Troksa1 and Kannan M. Krishnan1 1 University of Washington, Department of Materials Science and Engineering, United States Introduction: Magnetic particle imaging (MPI) is a real-time, quantitative and clinically safe imaging technique, potentially applicable for future clinical applications such as cancer imaging, cardiovascular imaging or stem cell labeling and tracking[1],[2]. MPI performance (i.e. spatial resolution and sensitivity) is highly dependent on nanoparticles (NPs) size distribution, magnetization and environment[3],[4]. Therefore, NPs MPI signal is different after distribution into tissues or binding to the cells. Here, using in vitro and in vivo studies, we present the potential capabilities of MPI for tissue targeted imaging applications such as cancer and atherosclerosis imaging. Materials and Methods: Monodispersed iron oxide nanoparticles (NPs) optimized for MPI were synthesized by thermal decomposition of iron oleate in the presence of oleic acid and transferred to water according to our previous reports[5]-[9]. Nanoparticles were functionalized using PMAO-PEG co-polymers and different PEG derivatives such as NH2-PEG-NH2 and NH2-PEG-SH (MWs: 2-20kDa). Cy5.5 near infra-red fluorescent (NIRF) molecules were conjugated to the NPs for multimodal (MPI/NIRF) imaging. For targeting experiments, the relevant targeting peptides (e.g. lactoferrin for targeting the C6 glioma xenografts in mice) were conjugated to the NPs[10]. All NPs formulations were characterized using dynamic light scattering (DLS), Zeta potential measurements, vibrating sample magnetometer (VSM) and transmission electron microscope (TEM). The biodistribution, pharmacokinetics and delivery of the NPs to organs and tissues (e.g. tumors and heart lesions) were evaluated using different groups of mice with brain or prostate cancers or aorta atherosclerosis. A home-built magnetic particle spectrometer (MPS) was used to evaluate the MPI performance of the NPs in tissues[4]. MPI, magnetic resonance imaging (MRI) and NIRF (IVIS) were used to monitor the biodistribution of the NPs in mice. Histology (H & E and Prussian Blue staining) were used to investigate tissue distribution and side-effects of the NPs. Results and Discussions: First, we used two preliminary experimental models to predict the MPI performance of the tracers in a tissue equivalent environment and an acidic lysosome-like solution[4],[7]. Then, for imaging of the reticuloendothelial system (RES) organs, cancers or heart lesions, we introduced functional groups (e.g. amine, -NH2) to the surface of the optimized NPs and used them as conjugation sites for bonding of the NIRF molecules (Cy5.5) and specific targeting peptides[8],[10]. We investigated the biodistribution (Fig. 1) of these NPs after their intravenous injection and evaluated their MPI performance after their accumulation in RES organs (e.g. liver and spleen) and other targeted tissues[5],[6]. Also, blood samples were collected by retro-orbital blood drawing and used for pharmacokinetic studies and evaluation of the NPs blood half-life. Our results show that MPI can be used as a potential whole-body imaging technique for a wide range of biomedical imaging applications. Also, NIRF has a high tracer mass sensitivity and reveals more details of microstructural distribution of these optimized MPI tracers in organs and tissues (e.g. cancers and heart lesions)[11]. Histology results showed no apparent side-effects due to accumulation of the NPs in organs. Fig.1. Multimodal MPI/NIRF/MRI imaging of the mice enabled us to map the biodistribution of the MPI tracers[5]. Conclusions: MPS and MPI enabled us to track our optimized MPI tracers in organs and targeted tissues effectively. Additional imaging modalities (NIRF and MRI) helped us to study the targeting ability, biodistribution and pharmacokinetics of the NPs in mice more accurately. These results pave the ways for future applications of MPI in pre-clinical tissue-targeted magnetic imaging and diagnostic applications. This work was supported by NIH grants 1RO1EB013689-01/NIBIB, 2R42EB013520-02A1 and 1R41EB013520-01.

Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications.

Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.

Nanoparticle contrast agents for computed tomography: a focus on micelles

Computed tomography (CT) is an X-ray-based whole-body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, owing to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing nontargeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade.

Targeted Labeling of Cancer Cells Using Biotin Tagged Avidin Functionalized Biocompatible Fluorescent Nanocrystals

The present study details the development of biotin tagged avidin functionalized Zinc Sulphide [ZnS] nanocrystals through a simple aqueous chemistry route at room temperature for targeted imaging applications. Surface functionalization of Manganese doped ZnS nanocrystals with L-cysteine provided functional groups that facilitated its conjugation to avidin. Further biotinylation of these particles through the strong non-covalent interaction between biotin and avidin enabled highly specific labeling of the biotin receptors on human hepatocellular carcinoma (HepG2) cells. The nanobioconjugates thus developed exhibited stable and brilliant fluorescence upon labeling the biotin receptors on cells as observed through fluorescence microscopy. Characterization studies using X-ray diffraction, dynamic light scattering as well as Fourier transform infrared spectroscopy revealed the bioconjugated particles to be appropriately functionalized and stable, with size ranging from 50 to 80 nm. Cytotoxicity of this material system evaluated using MTT, LDH leakage and apoptosis assay revealed its non-toxic nature even for high concentrations extending upto 250 microM and 48 hours of incubation. Our results confirmed that biotinylated ZnS nanocrystals offer great potential for highly specific labeling and targeted imaging of cancer cells.

Preparation of a Versatile Bifunctional Zeolite for Targeted Imaging Applications

Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1)-catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 ((68)Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile "clickable" zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities.

Conquering the dark side: colloidal iron oxide nanoparticles.

Nanomedicine approaches to atherosclerotic disease will have significant impact on the practice and outcomes of cardiovascular medicine. Iron oxide nanoparticles have been extensively used for nontargeted and targeted imaging applications based upon highly sensitive T2* imaging properties, which typically result in negative contrast effects that can only be imaged 24 or more hours after systemic administration due to persistent blood pool interference. Although recent advances involving MR pulse sequences have converted these dark contrast voxels into bright ones, the marked delays in imaging from persistent magnetic background interference and prominent dipole blooming effects of the magnetic susceptibility remain barriers to overcome. We report a T1-weighted (T1w) theranostic colloidal iron oxide nanoparticle platform, CION, which is achieved by entrapping oleate-coated magnetite particles within a cross-linked phospholipid nanoemulsion. Contrary to expectations, this formulation decreased T2 effects thus allowing positive T1w contrast detection down to low nanomolar concentrations. CION, a vascular constrained nanoplatform administered in vivo permitted T1w molecular imaging 1 h after treatment without blood pool interference, although some T2 shortening effects on blood, induced by the superparamagnetic particles, persisted. Moreover, CION was shown to encapsulate antiangiogenic drugs, like fumagillin, and retained them under prolonged dissolution, suggesting significant theranostic functionality. Overall, CION is a platform technology, developed with generally recognized as safe components, that overcomes the temporal and spatial imaging challenges associated with current iron oxide nanoparticle T2 imaging agents and which has theranostic potential in vascular diseases for detecting unstable ruptured plaque or treating atherosclerotic angiogenesis.

Spectral properties of a bifunctional PARACEST europium chelate: an intermediate for targeted imaging applications

This report describes a preliminary study to investigate the effect of structural variations in a bifunctional ligand being developed for targeted PARACEST applications. Utilizing Eu-DOTA-4AmCE as the functional PARACEST core, a nitro-aromatic functionality was incorporated to provide the point for conjugation. This intermediate possesses a coordinated water proton signal at 57 ppm which upon saturation produces a 22% decrease in bulk water signal intensity using 10 mM agent. Curve fitting analysis of the CEST spectrum to an exchange model based upon modified Bloch equations gave an estimate of 687 +/- 100 micros for the bound water lifetime (tau(m)). Although substantially longer than the 382 micros observed for the parent chelate structure, this water exchange rate remains in the necessary window to produce a significant CEST effect. These findings demonstrate the need to recognize the influence of bifunctional linkers on water exchange rates in lanthanide complexes of this type and the potential for using this functionality as a means of fine-tuning PARACEST performance.