Pharmacokinetic Profiling of Unlabeled Magnetic Nanoparticles Using Magnetic Particle Imaging as a Novel Cold Tracer Assay.

We present a magnetic particle imaging (MPI)-based assay for calculating the blood half-life and tissue uptake of magnetic nanoparticles (MNPs) without the need of labeling them. Dual-catheterized rats received 2.0 mg Fe of Synomag-D70, Synomag-D50, ferucarbotran, and Feraheme by femoral vein injection.

Cell-Penetrating and Enzyme-Responsive Peptides for Targeted Cancer Therapy: Role of Arginine Residue Length on Cell Penetration and In Vivo Systemic Toxicity.

For the improved delivery of cancer therapeutics and imaging agents, the conjugation of cell-penetrating peptides (CPPs) increases the cellular uptake and water solubility of agents. Among the various CPPs, arginine-rich peptides have been the most widely used. Combining CPPs with enzyme-responsive peptides presents an innovative strategy to target specific intracellular enzymes in cancer cells and when combined with the appropriate click chemistry can enhance theranostic drug delivery through the formation of intracellular self-assembled nanostructures.

Tumor-tropic Trojan horses: Using mesenchymal stem cells as cellular nanotheranostics.

Various classes of nanotheranostics have been developed for enhanced tumor imaging and therapy. However, key limitations for a successful use of nanotheranostics include their targeting specificity with limited off-site tissue accumulation as well as their distribution and prolonged retention throughout the entire tumor. Due to their inherent tumor-tropic properties, the use of mesenchymal stem cells (MSCs) as a "Trojan horse" has recently been proposed to deliver nanotheranostics more effectively.

A Smart Intracellular Self-Assembling Bioorthogonal Raman Active Nanoprobe for Targeted Tumor Imaging.

Inspired by the principle of in situ self-assembly, the development of enzyme-activated molecular nanoprobes can have a profound impact on targeted tumor detection. However, despite their intrinsic promise, obtaining an optical readout of enzyme activity with high specificity in native milieu has proven to be challenging. Here, a fundamentally new class of Raman-active self-assembling bioorthogonal enzyme recognition (nanoSABER) probes for targeted tumor imaging is reported.

Targeted Enzyme Activity Imaging with Quantitative Phase Microscopy.

Quantitative phase imaging (QPI) is a powerful optical imaging modality for label-free, rapid, and three-dimensional (3D) monitoring of cells and tissues. However, molecular imaging of important intracellular biomolecules such as enzymes remains a largely unexplored area for QPI. Herein, we introduce a fundamentally new approach by designing QPI contrast agents that allow sensitive detection of intracellular biomolecules.

Cellular Magnetic Imaging: Labeled vs. Unlabeled Cells.

Superparamagnetic iron oxide (SPIO)-labeling of cells has been applied for magnetic resonance imaging (MRI) cell tracking for over 30 years, having resulted in a dozen or so clinical trials. SPIO nanoparticles are biodegradable and can be broken down into elemental iron, and hence the tolerance of cells to magnetic labeling has been overall high. Over the years, however, single reports have accumulated demonstrating that the proliferation, migration, adhesion and differentiation of magnetically labeled cells may differ from unlabeled cells, with inhibition of chondrocytic differentiation of labeled human mesenchymal stem cells (hMSCs) as a notable example.

In Vivo Imaging of Naked and Microencapsulated Islet Cell Transplantation.

We describe step-by-step methods to label human pancreatic islet cells and murine insulinoma cells and their subsequent transplantation into type I diabetic mouse models with a focus on in vivo imaging using clinically applicable scanners. We also cover islets that are microencapsulated within alginate hydrogels loaded with imaging agents. By following these methods, it is possible to image cell grafts using T-weighted and T/T*-weighted H magnetic resonance imaging (MRI), F MRI, computed tomography, ultrasound imaging, and bioluminescence imaging in vivo.

Non-Invasive imaging of extracellular vesicles: Quo vaditis in vivo?

Extracellular vesicles (EVs) are lipid-bilayer delimited vesicles released by nearly all cell types that serve as mediators of intercellular signalling. Recent evidence has shown that EVs play a key role in many normal as well as pathological cellular processes. EVs can be exploited as disease biomarkers and also as targeted, cell-free therapeutic delivery and signalling vehicles for use in regenerative medicine and other clinical settings.

A 2D nanotheranostic platform based on graphene oxide and phase-change materials for bimodal CT/MR imaging, NIR-activated drug release, and synergistic thermo-chemotherapy.

Recent years have seen considerable progress in the development of nanomedicine by the advent of 2D nanomaterials serving as ideal platforms to integrate multiple theranostic functions. We synthesized multifunctional stimuli-responsive 2D-based smart nanocomposites (NCs), comprising gold nanoparticles (AuNPs) and superparamagnetic iron oxides (SPIOs) scaffolded within graphene oxide (GO) nanosheets, coated with doxorubicin (DOX)-loaded 1-tetradecanol (TD), and further modified with an alginate (Alg) polymer. TD is a phase-change material (PCM) that confines DOX molecules to the GO surface and melts when the temperature exceeds its melting point (m=39 °C), causing the PCM to release its drug payload.

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice.

Background: Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs).

Surface-enhanced Raman scattering: An emerging tool for sensing cellular function.

Continuous long-term intracellular imaging and multiplexed monitoring of biomolecular changes associated with key cellular processes remains a challenge for the scientific community. Recently, surface-enhanced Raman scattering (SERS) has been demonstrated as a powerful spectroscopic tool in the field of biology owing to its significant advantages. Some of these include the ability to provide molecule-specific information with exquisite sensitivity, working with small volumes of precious samples, real-time monitoring, and optimal optical contrast.

Opportunities for Molecular Imaging in Multiple Sclerosis Management: Linking Probe to Treatment.

Imaging has been a critical component of multiple sclerosis (MS) management for nearly 40 years. The visual information derived from structural MRI, that is, signs of blood-brain barrier disruption, inflammation and demyelination, and brain and spinal cord atrophy, are the primary metrics used to evaluate therapeutic efficacy in MS. The development of targeted imaging probes has expanded our ability to evaluate and monitor MS and its therapies at the molecular level.

Clinical magnetic hyperthermia requires integrated magnetic particle imaging.

Magnetic nanomaterials that respond to clinical magnetic devices have significant potential as cancer nanotheranostics. The complexities of their physics, however, introduce challenges for these applications. Hyperthermia is a heat-based cancer therapy that improves treatment outcomes and patient survival when controlled energy delivery is combined with accurate thermometry.

Enzyme-mediated intratumoral self-assembly of nanotheranostics for enhanced imaging and tumor therapy.

Enzyme-mediated intratumoral self-assembled (EMISA) nanotheranostics represent a new class of smart agents for combined imaging and therapy of cancer. Cancer cells overexpress various enzymes that are essential for high metabolism, fast proliferation, and tissue invasion and metastasis. By conjugating small molecules that contain an enzyme-specific cleavage site to appropriate chemical linkers, it is possible to induce self-assembly of nanostructures in tumor cells having the target enzyme.

In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI.

The tracking of the in vivo biodistribution of transplanted human mesenchymal stromal cells (hMSCs) relies on reporter genes or on the addition of exogenous imaging agents. However, reporter genes and exogenous labels may require bespoke manufacturing and regulatory processes if used in cell therapies, and the labels may alter the cells' properties and are diluted on cellular division. Here we show that high-mannose N-linked glycans, which are abundantly expressed on the surface of hMSCs, can serve as a biomarker for the label-free tracking of transplanted hMSCs by mannose-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI).

In Vivo Imaging of Implanted Hyaluronic Acid Hydrogel Biodegradation.

Although the use of stem cell therapy for central nervous system (CNS) repair has shown considerable promise, it is still limited by the immediate death of a large fraction of transplanted cells owing to cell handling procedures, injection stress and host immune attack leading to poor therapeutic outcomes. Scaffolding cells in hydrogels is known to protect cells from such immediate death by shielding them from mechanical damage and by averting an immune attack after transplantation. Implanted hydrogels must eventually degrade and facilitate a safe integration of the graft with the surrounding host tissue.

Multifunctional Theranostic Graphene Oxide Nanoflakes as MR Imaging Agents with Enhanced Photothermal and Radiosensitizing Properties.

The integration of multiple therapeutic and diagnostic functions into a single nanoplatform for image-guided cancer therapy has been an emerging trend in nanomedicine. We show here that multifunctional theranostic nanostructures consisting of superparamagnetic iron oxide (SPIO) and gold nanoparticles (AuNPs) scaffolded within graphene oxide nanoflakes (GO-SPIO-Au NFs) can be used for dual photo/radiotherapy by virtue of the near-infrared (NIR) absorbance of GO for photothermal therapy (PTT) and the Z element radiosensitization of AuNPs for enhanced radiation therapy (RT). At the same time, this nanoplatform can also be detected by magnetic resonance (MR) imaging because of the presence of SPIO NPs.

In Vivo MRI Tracking of Tumor Vaccination and Antigen Presentation by Dendritic Cells.

Cancer vaccination using tumor antigen-primed dendritic cells (DCs) was introduced in the clinic some 25 years ago, but the overall outcome has not lived up to initial expectations. In addition to the complexity of the immune response, there are many factors that determine the efficacy of DC therapy. These include accurate administration of DCs in the target tissue site without unwanted cell dispersion/backflow, sufficient numbers of tumor antigen-primed DCs homing to lymph nodes (LNs), and proper timing of immunoadjuvant administration.

Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System.

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces.

Imaging of Allografted Glial-Restricted Progenitor Cell Survival and Hydrogel Scaffold Biodegradation.

Transplanted glial-restricted progenitor (GRP) cells have potential to focally replace defunct astrocytes and produce remyelinating oligodendrocytes to avert neuronal death and dysfunction. However, most central nervous system cell therapeutic paradigms are hampered by high initial cell death and a host anti-graft immune response. We show here that composite hyaluronic acid-based hydrogels of tunable mechanical strengths can significantly improve transplanted GRP survival and differentiation.