Transformable Gallium-Based Liquid Metal Nanoparticles for Tumor Radiotherapy Sensitization.

The past decades have witnessed an increasing interest in the exploration of room temperature gallium-based liquid metal (LM) in the field of microfluidics, soft robotics, electrobiology, and biomedicine. Herein, this study for the first time reports the utilization of nanosized gallium-indium eutectic alloys (EGaIn) as a radiosensitizer for enhancing tumor radiotherapy. The sodium alginate (Alg) functionalized EGaIn nanoparticles (denoted as EGaIn@Alg NPs) are prepared via a simple one-step synthesis method. The coating of Alg not only prevents the aggregation and oxidation of EGaIn NPs in an aqueous solution but also enables them low cytotoxicity, good biocompatibility, and in-situ formation of gels in the Ca2+ enriched tumor physiological microenvironment. Due to the metallic nature and high density, EGaIn can increase the generation of reactive oxygen species under the irradiation of X-ray, which can not only directly promote DNA damage and cell apoptosis, but also show an efficient tumor inhibition rate in vivo. Moreover, EGaIn@Alg NPs hold good performance as computed tomography (CT) and photoacoustic tomography (PAT) imaging contrast agents. This work provides an alternative nanotechnology strategy for tumor radiosensitization and also enlarges the biomedical application of gallium-based LM.

A ROS-Sensitive Nanozyme-Augmented Photoacoustic Nanoprobe for Early Diagnosis and Therapy of Acute Liver Failure.

Early diagnosis of acute liver failure (ALF) is critical for curable treatment of patients, because most existing ALF therapies have narrow therapeutic time windows after disease onset. Reactive oxygen species (ROS), which lead to the sequential occurrences of hepatocyte necrosis and the leakage of alanine aminotransferase (ALT), represent early biomarkers of ALF. Photoacoustic imaging is emerging as a powerful tool for in vivo imaging of ROS. However, high-performance imaging probes that can boost the photoacoustic signals of the short-lived ROS of ALF are yet to be developed, and there remains a great challenge for ROS-based imaging of ALF. Herein, a ROS-sensitive nanozyme-augmented photoacoustic nanoprobe for successful in vivo imaging of ALF is presented. The deep-penetrating photoacoustic signals of the nanoprobe can be activated by the overexpressed ROS in ALF due to the synergy between nanocatalytic bubbles generation and thermoelastic expansion. Impressively, the nanozyme-augmented ROS imaging enables earlier diagnosis of ALF than the clinical ALT method, and the ROS-activated catalytic activity of nanoprobe permits timely nanocatalytic therapy of ALF.

Dynamic nanoassemblies for imaging and therapy of neurological disorders.

The past decades have witnessed an increased incidence of neurological disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and epilepsy, which significantly lower patients' life quality and increase the economic and social burden. Recently, nanomedicines composed of imaging and/or therapeutic agents have been explored to diagnose and/or treat NDs due to their enhanced bioavailability, blood-brain barrier (BBB) permeability, and targeting capacity. Intriguingly, dynamic nanoassemblies self-assembled from functional nanoparticles to simultaneously interfere with multiple pathogenic substances and pathological changes, have been regarded as one of the foremost candidates to improve the diagnostic and therapeutic efficacy of NDs. To help readers better understand this emerging field, in this review, the pathogenic mechanism of different types of NDs is briefly introduced, then the functional nanoparticles used as building blocks in the construction of dynamic nanoassemblies for NDs theranostics are summarized. Furthermore, dynamic nanoassemblies that can actively cross the BBB to target brain lesions, sensitively and efficiently diagnose or treat NDs, and effectively promote neuroregeneration are highlighted. Finally, we conclude with our perspectives on the future development in this field.

Dynamic nanoassembly-based drug delivery system (DNDDS): Learning from nature.

Dynamic nanoassembly-based drug delivery system (DNDDS) has evolved from being a mere curiosity to emerging as a promising strategy for high-performance diagnosis and/or therapy of various diseases. However, dynamic nano-bio interaction between DNDDS and biological systems remains poorly understood, which can be critical for precise spatiotemporal and functional control of DNDDS in vivo. To deepen the understanding for fine control over DNDDS, we aim to explore natural systems as the root of inspiration for researchers from various fields. This review highlights ingenious designs, nano-bio interactions, and controllable functionalities of state-of-the-art DNDDS under endogenous or exogenous stimuli, by learning from nature at the molecular, subcellular, and cellular levels. Furthermore, the assembly strategies and response mechanisms of tailor-made DNDDS based on the characteristics of various diseased microenvironments are intensively discussed. Finally, the current challenges and future perspectives of DNDDS are briefly commented.

Microenvironment-tailored nanoassemblies for the diagnosis and therapy of neurodegenerative diseases.

Neurodegenerative disorder is an illness involving neural dysfunction/death attributed to complex pathological processes, which eventually lead to the mortality of the host. It is generally recognized through features such as mitochondrial dysfunction, protein aggregation, oxidative stress, metal ions dyshomeostasis, membrane potential change, neuroinflammation and neurotransmitter impairment. The aforementioned neuronal dysregulations result in the formation of a complex neurodegenerative microenvironment (NME), and may interact with each other, hindering the performance of therapeutics for neurodegenerative disease (ND). Recently, smart nanoassemblies prepared from functional nanoparticles, which possess the ability to interfere with different NME factors, have shown great promise to enhance the diagnostic and therapeutic efficacy of NDs. Herein, this review highlights the recent advances of stimuli-responsive nanoassemblies that can effectively combat the NME for the management of ND. The first section outlined the NME properties and their interrelations that are exploitable for nanoscale targeting. The discussion is then extended to the controlled assembly of functional nanoparticles for the construction of stimuli-responsive nanoassemblies. Further, the applications of stimuli-responsive nanoassemblies for the enhanced diagnosis and therapy of ND are introduced. Finally, perspectives on the future development of NME-tailored nanomedicines are given.

Safety Assessment of Nanomaterials to Eyes: An Important but Neglected Issue.

The production and application of nanomaterials have grown tremendously during last few decades. The widespread exposure of nanoparticles to the public is provoking great concerns regarding their toxicity to the human body. However, in comparison with the extensive studies carried out to examine nanoparticle toxicity to the human body/organs, one especially vulnerable organ, the eye, is always neglected. Although it is a small part of the body, 90% of outside information is obtained via the ocular system. In addition, eyes usually directly interact with the surrounding environment, which may get severer damage from toxic nanoparticles compared to inner organs. Therefore, the study of assessing the potential nanoparticle toxicity to the eyes is of great importance. Here, the recent advance of some representative manufactured nanomaterials on ocular toxicity is summarized. First, a brief introduction of ocular anatomy and disorders related to particulate matter exposure is presented. Following, the factors that may influence toxicity of nanoparticles to the eye are emphasized. Next, the studies of representative manufactured nanoparticles on eye toxicity are summarized and classified. Finally, the limitations that are associated with current nanoparticle-eye toxicity research are proposed.

Bi2WO6 Semiconductor Nanoplates for Tumor Radiosensitization through High- Z Effects and Radiocatalysis.

The radioresistance of tumor cells is considered to be an Achilles' heel of cancer radiotherapy. Thus, an effective and biosafe radiosensitizer is highly desired but hitherto remains a big challenge. With the rapid progress of nanomedicine, multifunctional inorganic nanoradiosensitizers offer a new route to overcome the radioresistance and enhance the efficacy of radiotherapy. Herein, poly(vinylpyrrolidone) (PVP)-modified Bi2WO6 nanoplates with good biocompatibility were synthesized through a simple hydrothermal process and applied as a radiosensitizer for the enhancement of radiotherapy for the first time. On the one hand, the high- Z elements Bi ( Z = 83) and W ( Z = 74) endow PVP-Bi2WO6 with better X-ray energy deposition performance and thus enhance radiation-induced DNA damages. On the other hand, Bi2WO6 semiconductors exhibit significant photocurrent and photocatalytic-like radiocatalytic activity under X-ray irradiation, giving rise to the effective separation of electron/hole (e-/h+) pairs and subsequently promoting the generation of cytotoxic reactive oxygen species, especially hydroxyl radicals (•OH). The γ-H2AX and clonogenic assays demonstrated that PVP-Bi2WO6 could efficiently increase cellular DNA damages and colony formations under X-ray irradiation. These versatile features endowed PVP-Bi2WO6 nanoplates with enhanced radiotherapy efficacy in animal models. In addition, Bi2WO6 nanoplates can also serve as good X-ray computed tomography imaging contrast agents. Our findings provide an alternative nanotechnology strategy for tumor radiosensitization through simultaneous radiation energy deposition and radiocatalysis.

Mass production of poly(ethylene glycol) monooleate-modified core-shell structured upconversion nanoparticles for bio-imaging and photodynamic therapy.

Developing robust and high-efficient synthesis approaches has significant importance for the expanded applications of upconversion nanoparticles (UCNPs). Here, we report a high-throughput synthesis strategy to fabricate water-dispersible core-shell structured UCNPs. Firstly, we successfully obtain more than 10 grams core UCNPs with high quality from one-pot reaction using liquid rare-earth precursors. Afterwards, different core-shell structured UCNPs are fabricated by successive layer-by-layer strategy to get enhanced fluorescence property. Finally, the hydrophobic UCNPs are modified with poly(ethylene glycol) monooleate (PEG-OA) though a novel physical grinding method. On the basis of mass-production, we use the as-prepared PEG-UCNPs to construct an 808-nm stimuli photodynamic therapy agent, and apply them in cancer therapy and bio-imaging.

Recent advances of stimuli-responsive systems based on transition metal dichalcogenides for smart cancer therapy.

Stimuli-responsive systems, which can be used for temporally and spatially controllable therapeutic platforms, have been widely investigated in cancer therapy. Among a wide range of stimuli-responsive nanomaterials, transition metal dichalcogenides (TMDCs) have recently attracted great attention due to their large surface-to-volume ratio, atomic thickness, and other unique physicochemical properties. Thus, TMDCs are able to be responsive to various endogenous (e.g. acidic pH and overexpressed enzymes) or exogenous stimuli (e.g. light and magnetic). The majority of TMDC-based therapeutic platforms are triggered by near-infrared (NIR) light. However, due to the limited penetration of NIR light, novel strategies that are able to ablate deep-seated tumor tissues have emerged in recent years and have been applied to design multi-stimuli-responsive nano-systems. A comprehensive overview of the development of stimuli-responsive TMDC-based nanoplatforms for "smart" cancer therapy is presented to demonstrate a more intelligent and better controllable therapeutic strategy. Furthermore, the versatile properties of TMDCs and the typical responsive principles of certain stimuli-responsive platforms are discussed for a better understanding of selected examples in this review.

Emerging Strategies of Nanomaterial-Mediated Tumor Radiosensitization.

Nano-radiosensitization has been a hot concept for the past ten years, and the nanomaterial-mediated tumor radiosensitization method is mainly focused on increasing intracellular radiation deposition by high atomic number (high Z) nanomaterials, particularly gold (Au)-mediated radiation enhancement. Recently, various new nanomaterial-mediated radiosensitive approaches have been successively reported, such as catalyzing reactive oxygen species (ROS) generation, consuming intracellular reduced glutathione (GSH), overcoming tumor hypoxia, and various synergistic radiotherapy ways. These strategies may open a new avenue for enhancing the radiotherapeutic effect and avoiding its side effects. Nevertheless, reviews systematically summarizing these newly emerging methods and their radiosensitive mechanisms are still rare. Therefore, the general strategies of nanomaterial-mediated tumor radiosensitization are comprehensively summarized, particularly aiming at introducing the emerging radiosensitive methods. The strategies are divided into three general parts. First, methods on account of the intrinsic radiosensitive properties of nanoradiosensitizers for radiosensitization are highlighted. Then, newly developed synergistic strategies based on multifunctional nanomaterials for enhancing radiotherapy efficacy are emphasized. Third, nanomaterial-mediated radioprotection approaches for increasing the radiotherapeutic ratio are discussed. Importantly, the clinical translation of nanomaterial-mediated tumor radiosensitization is also covered. Finally, further challenges and outlooks in this field are discussed.

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life.

INTRODUCTION: Silica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period. MATERIALS AND METHODS: Herein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults. RESULTS: SiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment. DISCUSSION: These findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood.

Toxicity of silicon dioxide nanoparticles with varying sizes on the cornea and protein corona as a strategy for therapy.

The human cornea is exposed directly to particulate matter (PM) in polluted air. This exposure can cause eye discomfort and corneal injury. Ultrafine PM (diameter <100 nm) is thought to be particularly harmful to health, but there is limited research investigating its toxicity to the eye. In this study, we evaluated toxicity differences among 30-, 40-, 100- and 150-nm silicon dioxide nanoparticles (SiO2 NPs) on the cornea. A 24-hour in vitro exposure of primary human corneal epithelial cells (hCECs) to ultrafine (30 and 40 nm) SiO2 NPs produced toxicity, as evidenced by cell membrane damage, reduced cell viability, increased cell death and mitochondrial dysfunction. In vivo exposure to the same nanoparticles produced observable corneal injury. These effects were more severe with ultrafine than with fine (100 and 150 nm) SiO2 NPs. Common antioxidant compounds, e.g., glutathione, did not protect the cornea from SiO2 NP-induced damage. However, foetal bovine serum (FBS) did significantly reduce toxicity, likely by forming a protective protein corona around the nanoparticles. This finding suggests that FBS (or its derivatives) may be a useful clinical therapy for corneal toxicity caused by ultrafine particulates.

Therapeutic Nanoparticles Based on Curcumin and Bamboo Charcoal Nanoparticles for Chemo-Photothermal Synergistic Treatment of Cancer and Radioprotection of Normal Cells.

Low water solubility, extensive metabolism, and drug resistance are the existing unavoidable disadvantages of the insoluble drug curcumin in biomedical applications. Herein, we employed d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-functionalized near-infrared (NIR)-triggered photothermal mesoporous nanocarriers with bamboo charcoal nanoparticles (TPGS-BCNPs) to load and deliver curcumin for improving its bioavailability. This system could considerably increase the accumulation of curcumin in cancer cells for enhanced curcumin bioavailability via simultaneously promoting the cellular internalization of the as-synthesized composite (TPGS-BCNPs@curcumin) by the size effect of NPs and considerably triggering controlled curcumin release from TPGS-BCNPs@curcumin by NIR stimulation and reducing efflux of curcumin by the P-glycoprotein (P-gp) inhibition of TPGS, so as to enhance the therapeutic effect of curcumin and realize a better chemo-photothermal synergetic therapy in vitro and in vivo. Besides cancer therapy, studies indicated that curcumin and some carbon materials could be used as radical scavengers that play an important role in the radioprotection of normal cells. Hence, we also investigated the free-radical-scavenging ability of the TPGS-BCNPs@curcumin composite in vitro to preliminarily evaluate its radioprotection ability for healthy tissues. Therefore, our work provides a multifunctional delivery system for curcumin bioavailability enhancement, chemo-photothermal synergetic therapy of cancer, and radioprotection of healthy tissues.

Two-dimensional transition metal dichalcogenide nanomaterials for combination cancer therapy.

As demonstrated by preclinical and clinical studies, it is often difficult to eradicate tumors, particularly those that are deep-located, with photothermal therapy (PTT) alone because of the intrinsic drawbacks of optical therapy. To increase the therapeutic effect of PTT and reduce its significant side-effects, a new direction involving the combination of PTT with other therapeutic techniques is highly desirable. Recently, two-dimensional (2D) transition metal dichalcogenides (TMDCs), the typical ultrathin 2D layer nanomaterials, have gained tremendous interest in many different fields including biomedicine, due to their novel physicochemical properties. Benefitting from their intrinsic near-infrared absorbance properties and extremely large specific surface areas, many efforts are being devoted to fabricating 2D TMDC-based multifunctional nanoplatforms for combining PTT with other therapeutics in order to realize 2D TMDC-assisted combination therapy and thus achieve excellent anti-tumor therapeutic efficacy. In addition, various inorganic nanoparticles and fluorescent probes can be attached to the surface of 2D TMDCs to obtain nanocomposites with versatile optical and/or magnetic properties that are useful for multi-modal imaging and imaging-guided cancer therapy. In this review, we mainly summarize the latest advances in the utilization of 2D TMDCs for PTT combination cancer therapy, including PTT/photodynamic therapy, PTT/chemotherapy, PTT/radiotherapy, PTT/gene therapy, and imaging-guided cancer combination therapy, as well as the evaluation of their behaviors and toxicology both in vitro and in vivo. Furthermore, we address the principle for the design of 2D TMDC-assisted photothermal combination theranostics and the future prospects and challenges of using 2D TMDC-based nanomaterials for theranostic applications.