Light-Armed Nitric Oxide-Releasing Micromotor .

The delivery of NO at a high spatiotemporal precision is important but still challenging for existing NO-releasing platforms due to the lack of precise motion control and limited biomedical functions. In this work, we propose an alternative strategy for developing the light-armed nitric oxide-releasing micromotor (LaNorM), in which a main light beam was employed to navigate the microparticle and stimulate NO release and an auxiliary light beam was used to cooperate with the released NO to act as a remotely controlled scalpel for cell separation. Benefiting from the advantages of fully controlled locomotion, photostimulated NO release, and microsurgery ability at the single-cell level, the proposed LaNorM could enable a series of biomedical applications , including the separation of flowing emboli, selective removal of a specific thrombus, and inhibition of thrombus growth, which may provide new insight into the precise delivery of NO and the treatment of cardiovascular diseases.

Semiphysical Design Concept for Developing Miniaturized Microrobots .

The miniaturization of biomedical microrobots is crucial for their applications. However, it is challenging to reduce their size while maintaining their biomedical functions. To resolve this contradiction, we propose a semiphysical design concept for developing miniaturized microrobots, in which invisible components such as light beams are utilized to replace most of the physical parts of a microrobot, thus minimizing its physical size without sacrificing its biomedical functions.

Discovery of Natural Products Alleviating Renal Fibrosis with a Viscosity-Responsive Molecular Probe.

Renal fibrosis poses a significant threat to individuals suffering from chronic progressive kidney disease. Given the absence of effective medications for treating renal fibrosis, it becomes crucial to assess the extent of fibrosis in real time and explore the development of novel drugs with substantial therapeutic benefits. Due to the accumulation of renal tissue damage and the uncontrolled deposition of fibrotic matrix during the course of the disease, there is an increase in viscosity both intracellularly and extracellularly.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity.

Fully Active Delivery of Nanodrugs In Vivo via Remote Optical Manipulation.

The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles.

Optically Programmable Living Microrouter in Vivo.

With high reconfigurability and swarming intelligence, programmable medical micromachines (PMMs) represent a revolution in microrobots for executing complex coordinated tasks, especially for dynamic routing of various targets along their respective routes. However, it is difficult to achieve a biocompatible implantation into the body due to their exogenous building blocks. Herein, a living microrouter based on an organic integration of endogenous red blood cells (RBCs), programmable scanning optical tweezers and flexible optofluidic strategy is reported.

Acid and Hypoxia Tandem-Activatable Deep Near-Infrared Nanoprobe for Two-Step Signal Amplification and Early Detection of Cancer.

The early detection of cancers can significantly change outcomes even with existing treatments. However, ~50% of cancers still cannot be detected until they reach an advanced stage, highlighting the great challenges in the early detection. Here, an ultrasensitive deep near-infrared (dNIR) nanoprobe that is successively responsive to tumor acidity and hypoxia is reported.

An Optically Controlled Virtual Microsensor for Biomarker Detection In Vivo.

Current technologies for the real-time analysis of biomarkers in vivo, such as needle-type microelectrodes and molecular imaging methods based on exogenous contrast agents, are still facing great challenges in either invasive detection or lack of active control of the imaging probes. In this study, by combining the design concepts of needle-type microelectrodes and the fluorescence imaging method, a new technique is developed for detecting biomarkers in vivo, named as "optically controlled virtual microsensor" (OCViM). OCViM is established by the organic integration of a specially shaped laser beam and fluorescent nanoprobe, which serve as the virtual handle and sensor tip, respectively.

Optically Manipulated Neutrophils as Native Microcrafts .

As the first line of host defense against invading pathogens, neutrophils have an inherent phagocytosis capability for the elimination of foreign agents and target loading upon activation, as well as the ability to transmigrate across blood vessels to the infected tissue, making them natural candidates to execute various medical tasks . However, most of the existing neutrophil-based strategies rely on their spontaneous chemotactic motion, lacking in effective activation, rapid migration, and high navigation precision. Here, we report an optically manipulated neutrophil microcraft through the organic integration of endogenous neutrophils and scanning optical tweezers, functioning as a native biological material and wireless remote controller, respectively.

Small-Molecule Photoacoustic Imaging Probe with Aggregation-Enhanced Amplitude for Real-Time Visualization of Acute Kidney Injury.

Acute kidney injury (AKI) has become a growing issue for patients with the extensive use of all kinds of drugs in clinic. Photoacoustic (PA) imaging provides a noninvasive and real-time imaging method for studying kidney injury, but it has inherent shortages in terms of high background signal and low detection sensitivity for exogenous imaging agents. Intriguingly, J-aggregation offers to tune the optical properties of the dyes, thus providing a platform for developing new PA probes with desired performance.

Multiparameter Longitudinal Imaging of Immune Cell Activity in Chimeric Antigen Receptor T Cell and Checkpoint Blockade Therapies.

Longitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for the assessment of cytotoxic T lymphocyte mediated cancer cell killing. G-SNAT was found to specifically detect the activity of granzyme B within the cytotoxic granules of activated T cells and engaged cancer cells .

Renal-clearable and biodegradable black phosphorus quantum dots for photoacoustic imaging of kidney dysfunction.

The kidney is a vital organ and susceptible to various diseases. Photoacoustic (PA) imaging provides a powerful technique for studying kidney dysfunction, for which many smart photoacoustic imaging agents have been developed. But the complete clearance of the introduced contrast agents after imaging remains to be challenging, leading to long-term toxicity concerns.

Reversibly Photoswitching Upconversion Nanoparticles for Super-Sensitive Photoacoustic Molecular Imaging.

Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle-based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice.

Tumor Microenvironment-Regulated and Reported Nanoparticles for Overcoming the Self-Confinement of Multiple Photodynamic Therapy.

The efficiency of photodynamic therapy (PDT) highly depends on the tumor oxygenation state. However, PDT itself can not only cause oxygen depletion but also prevent oxygen supply in tumors. Such self-confinement effect significantly limits the efficacy of PDT, especially fractionated PDT (fPDT).

Carbon-coated FeCo nanoparticles as sensitive magnetic-particle-imaging tracers with photothermal and magnetothermal properties.

The low magnetic saturation of iron oxide nanoparticles, which are developed primarily as contrast agents for magnetic resonance imaging, limits the sensitivity of their detection using magnetic particle imaging (MPI). Here, we show that FeCo nanoparticles that have a core diameter of 10 nm and bear a graphitic carbon shell decorated with poly(ethylene glycol) provide an MPI signal intensity that is sixfold and fifteenfold higher than the signals from the superparamagnetic iron oxide tracers VivoTrax and Feraheme, respectively, at the same molar concentration of iron. We also show that the nanoparticles have photothermal and magnetothermal properties and can therefore be used for tumour ablation in mice, and that they have high optical absorbance in a broad near-infrared region spectral range (wavelength, 700-1,200 nm), making them suitable as tracers for photoacoustic imaging.

Exploring the Condensation Reaction between Aromatic Nitriles and Amino Thiols To Optimize In Situ Nanoparticle Formation for the Imaging of Proteases and Glycosidases in Cells.

The condensation reaction between 6-hydroxy-2-cyanobenzothiazole (CBT) and cysteine has been shown for various applications such as site-specific protein labelling and in vivo cancer imaging. This report further expands the substrate scope of this reaction by varying the substituents on aromatic nitriles and amino thiols and testing their reactivity and ability to form nanoparticles for cell imaging. The structure-activity relationship study leads to the identification of the minimum structural requirement for the macrocyclization and assembly process in forming nanoparticles.

A Near-Infrared Phosphorescent Nanoprobe Enables Quantitative, Longitudinal Imaging of Tumor Hypoxia Dynamics during Radiotherapy.

Hypoxia plays a key role in tumor resistance to radiotherapy. It is important to study hypoxia dynamics during radiotherapy to improve treatment planning and prognosis. Here, we describe a luminescent nanoprobe, composed of a fluorescent semiconducting polymer and palladium complex, for quantitative longitudinal imaging of tumor hypoxia dynamics during radiotherapy.

A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice.

Multimodality imaging involves the use of more imaging modes to image the same living subjects and is now generally preferred in clinics for cancer imaging. Here we present multimodality-Magnetic Particle Imaging (MPI), Magnetic Resonance Imaging (MRI), Photoacoustic, Fluorescent-nanoparticles (termed MMPF NPs) for imaging tumor xenografts in living mice. MMPF NPs provide long-term (more than 2 months), dynamic, and accurate quantification, , of NPs and in real time by MPI.

Magnetic Particle Imaging in Neurosurgery.

Background: Magnetic particle imaging (MPI) is a novel radiation-free tomographic imaging method that provides a background-free, signal attenuation-free, direct quantification of the spatial distribution of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal resolution (milliseconds), high spatial resolution (<1 mm), and extreme sensitivity (μmol). The technique is based on nonlinear magnetization of the SPIONs when exposed to an oscillating magnetic field. MPI was first described in 2001.

Janus Iron Oxides @ Semiconducting Polymer Nanoparticle Tracer for Cell Tracking by Magnetic Particle Imaging.

Iron oxides nanoparticles tailored for magnetic particle imaging (MPI) have been synthesized, and their MPI signal intensity is three-times that of commercial MPI contrast (Ferucarbotran, also called Vivotrax) and seven-times that of MRI contrast (Feraheme) at the same Fe concentration. MPI tailored iron oxide nanoparticles were encapsulated with semiconducting polymers to produce Janus nanoparticles that possessed optical and magnetic properties for MPI and fluorescence imaging. Janus particles were applied to cancer cell labeling and in vivo tracking, and as few as 250 cells were imaged by MPI after implantation, corresponding to an amount of 7.

Core-Shell MnSe@Bi2 Se3 Fabricated via a Cation Exchange Method as Novel Nanotheranostics for Multimodal Imaging and Synergistic Thermoradiotherapy.

MnSe@Bi2 Se3 core-shell nanostructures with highly integrated imaging and therapy functions are fabricated by a simple cation exchange method. Using those nanoparticles as a theranostic agent, a promise concept is further demonstrated to enhance conventional radiotherapy by: i) using X-ray absorbing agents to locally concentrate radiation energy and ii) employing near-infrared-light-triggered photothermal therapy to overcome hypoxia-associated radioresistance.

Tracking Cancer Metastasis In Vivo by Using an Iridium-Based Hypoxia-Activated Optical Oxygen Nanosensor.

We have developed a nanosensor for tracking cancer metastasis by noninvasive real-time whole-body optical imaging. The nanosensor is prepared by the formation of co-micelles from a poly(N-vinylpyrrolidone)-conjugated iridium(III) complex (Ir-PVP) and poly(ε-caprolactone)-b-poly(N-vinylpyrrolidone) (PCL-PVP). The near-infrared phosphorescence emission of the nanosensor could be selectively activated in the hypoxic microenvironment induced by cancer cells.

Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo.

Highly sensitive and specific non-invasive molecular imaging methods are particularly desirable for the early detection of cancers. Here we report a near-infrared optical imaging probe highly specific to the hypoxic tumour microenvironment to detect tumour and cancer cells with the sensitivity to a few thousands cancer cells. This oxygen-sensitive, near-infrared emitting and water-soluble phosphorescent macromolecular probe can not only report the hypoxic tumour environment of various cancer models, including metastatic tumours in vivo, but can also detect a small amount of cancer cells before the formation of the tumour based on the increased oxygen consumption during cancer cell proliferation.

Near-Infrared Emitting Gold Cluster-Poly(acrylic acid) Hybrid Nanogels.

A facile synthesis of near-infrared (NIR) luminescent gold cluster-poly(acrylic acid) (PAA) hybrid nanogels was developed by in situ reduction of gold salt in the core-hollow and shell-porous PAA nanogels. These Au-PAA nanogels exhibited excellent near-infrared photoluminescence properties and showed targeting potential in the optical imaging of the living body.

Near-IR-triggered photothermal/photodynamic dual-modality therapy system via chitosan hybrid nanospheres.

Gold nanorods (AuNR)- and indocyanine green (ICG)-encapsulated chitosan hybrid nanospheres (CS-AuNR-ICG NSs) were successfully prepared and used for photothermal and photodynamic combined therapy with a single irradiation. These nanospheres were characterized by transmission electron microscopy, dynamic light scattering and UV-Vis absorption spectra. The in vivo anticancer effects of the hybrid nanospheres were examined by photodynamic therapy (PDT), photothermal therapy (PTT), and PTT/PDT combined therapy.