A D-Y Shaped Neuropeptide Y Mimetic Peptide-Dye Self-Assembly with Maximal Emission Beyond 1300 nm and Glioma Mitochondrial Activity Modulation.

Neuropeptide Y (NPY), as one of the most abundant neuropeptides known, is widely distributed in the central and peripheral nervous system. However, most of the reported NPY-mimetic peptides are hard to cross the blood-brain barrier, target glioma mitochondria, and achieve self-assembly nanostructure in situ. Here, based on the α-helix structure of the novel chiral NPY-mimetic peptides D/LNPY(14), a Y-shaped peptide is designed with the sequences that can be recognized by enterokinase and achieved nanofibers conversion in glioma cell mitochondria. Coupling the Y-shaped NPY-mimetic peptide with the NIR-II fluorophore IR1048, a red-shifting of the fluorescence spectrum beyond 1300 nm is achieved through self-assembly. After the self-assembly in glioma mitochondria, the formed nanofibers can promote intracellular mitochondrial ROS production and extend the NIR-II fluorescence imaging time to at least 7 days in vivo. This work for the first time endows the self-assembly of α-helical-based chiral NPY-mimetic peptides, providing a novel strategy for glioma subcellular regulation enhanced antitumor treatment guided by NIR-II fluorescence imaging.

A Contrast-Enhanced Tri-Modal MRI Technique for High-Performance Hypoxia Imaging of Breast Cancer.

Personalized radiotherapy strategies enabled by the construction of hypoxia-guided biological target volumes (BTVs) can overcome hypoxia-induced radioresistance by delivering high-dose radiotherapy to targeted hypoxic areas of the tumor. However, the construction of hypoxia-guided BTVs is difficult owing to lack of precise visualization of hypoxic areas. This study synthesizes a hypoxia-responsive T1 , T2 , T2 mapping tri-modal MRI molecular nanoprobe (SPION@ND) and provides precise imaging of hypoxic tumor areas by utilizing the advantageous features of tri-modal magnetic resonance imaging (MRI). SPION@ND exhibits hypoxia-triggered dispersion-aggregation structural transformation. Dispersed SPION@ND can be used for routine clinical BTV construction using T1 -contrast MRI. Conversely, aggregated SPION@ND can be used for tumor hypoxia imaging assessment using T2 -contrast MRI. Moreover, by introducing T2 mapping, this work designs a novel method (adjustable threshold-based hypoxia assessment) for the precise assessment of tumor hypoxia confidence area and hypoxia level. Eventually this work successfully obtains hypoxia tumor target and accurates hypoxia tumor target, and achieves a one-stop hypoxia-guided BTV construction. Compared to the positron emission tomography-based hypoxia assessment, SPION@ND provides a new method that allows safe and convenient imaging of hypoxic tumor areas in clinical settings.

Harnessing the Potential of a Nitroreductase-Responsive Fluorescent Probe for the Diagnosis of Bacterial Keratitis.

Bacterial keratitis, an ocular emergency, is the predominant cause of infectious keratitis. However, diagnostic procedures for it are invasive, time-consuming, and expeditious, thereby limiting effective treatment for the disease in the clinic. It is imperative to develop a timely and convenient method for the noninvasive diagnosis of bacterial keratitis. Fluorescence imaging is a convenient and noninvasive diagnostic method with high sensitivity. In this study, a type of nitroreductase-responsive probe (NTRP), which responds to nitroreductase to generate fluorescence signals, was developed as an activatable fluorescent probe for the imaging diagnosis of bacterial keratitis. Imaging experiments both in vitro and in vivo demonstrated that the probe exhibited "turn-on" fluorescence signals in response to nitroreductase-secreting bacteria within 10 min. Furthermore, the fluorescence intensity reached its highest at 4 or 6 h in vitro and at 30 min in vivo when the excitation wavelength was set at 520 nm. Therefore, the NTRP has the potential to serve as a feasible agent for the rapid and noninvasive in situ fluorescence diagnosis of bacterial keratitis.

Amorphous Nitrogen-Doped Carbon Nanocages with Excellent SERS Sensitivity and Stability for Accurate Identification of Tumor Cells.

The surface-enhanced Raman scattering (SERS) bioprobe's strategy for identifying tumor cells always depended on the intensity difference of the Raman signal compared with that of normal cells. Hence, exploring novel SERS nanostructure with excellent spectra stability, a high enhancement factor (EF), and good biocompatibility is a primary premise for boosting SERS signal reliability and accuracy of tumor cells. Here, high SERS EF (5.52 × 106) is acquired by developing novel amorphous nitrogen-doped carbon (NDC) nanocages (NCs), whose EF value was in a leading position among carbon-based SERS substrates. In addition, a uniform SERS signal was obtained on NDC NCs due to homogeneous morphology and size. The delocalized carbon-conjugated systems of graphitic-N, pyrrole-N, and pyridine-N with lone pair electrons increase the electronic density of states and reduce the electron localization function of NDC NCs, thereby promoting the charge transfer process. The electron-donor platform of the NDC NCs facilitates the thermodynamic process of charge transfer, resulting in multimode vibrational coupling in the surface complexes, which greatly amplifies the molecular polarizability. Importantly, the good biocompatibility and signal stability endow these NDC NC SERS bioprobes unique superiority in distinguishing tumor cells, and quantitative recognition of two triple-negative breast cancer cells based on SERS detection mode has been successfully realized.

EGFR-Targeted Liposomes Combined with Ginsenoside Rh2 Inhibit Triple-Negative Breast Cancer Growth and Metastasis.

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype due to its lack of targeted therapies and poor prognosis. In order to treat patients with these tumors, efforts have been made to explore feasible targets. Epidermal growth factor receptor (EGFR)-targeted therapy is currently in clinical trials and regarded to be a promising treatment strategy. In this study, an EGFR-targeting nanoliposome (LTL@Rh2@Lipo-GE11) using ginsenoside Rh2 as a wall material was developed, in which GE11 was used as the EGFR-binding peptide to deliver more ginsenoside Rh2 and luteolin into TNBC. In comparison to non-targeted liposomes (Rh2@Lipo and LTL@Rh2@Lipo), the nanoliposomes LTL@Rh2@Lipo-GE11 demonstrated a high specificity to MDA-MB-231 cells that expressed a high level of EGFR both in vitro and in vivo, contributing to the strong inhibitory effects on the growth and migration of TNBC. These results suggest that LTL@Rh2@Lipo-GE11 is a prospective candidate for targeted therapy of TNBC, with a remarkable capability to inhibit tumor development and metastasis.

One-step rapid colorimetric detection of K+ using silver nanoparticles modified by crown ether.

Urinary potassium is an important parameter in clinical health diagnosis. Rapid and convenient detection of potassium ions (K+) in urine is essential for personal healthcare and health management. Here, crown ether (4-aminodibenzo-18-crown-6, ADC) modified silver nanoparticles (ADC-Ag NPs) were successfully prepared for one-step rapid colorimetric detection of urinary potassium. The detection mechanism is as follows: due to the matching sizes of the diameter of K+ and the cavity in crown ether 6, K+ is encapsulated between the cavities of two crown ethers, resulting in the clumping of ADC-Ag NPs and the color of the solution being altered. The colorimetric detection method has a fast response and is completed within 20 minutes. It also shows good selectivity and interference immunity. The lowest detectable concentration is 20 µM with the naked eye and 2.16 µM for UV-vis absorption spectroscopy. A good linear relationship (R2 = 0.9931) between the absorption intensity ratio and K+ concentration (0-100 µM) indicates that this colorimetric probe can be used to detect K+. The method was also applied for quantitative analysis of K+ in real urine samples with recovery between 116 and 120%.

Multifunctional Modulation of High-Performance Znx Fe3-x O4 Nanoparticles by Precisely Tuning the Zinc Doping Content.

The possibility to precisely control important properties of nanoparticles (NPs) such as their size, morphology, surface charge, or doping content is crucial for enhancing the performance of existing solutions beyond the state-of-the-art and for enabling novel applications. In this work, custom-tailored Znx Fe3- x O4 NPs are synthesized at different Zn doping concentrations to augment and expand their usefulness for high-performance applications in nanomedicine. By precisely increasing the Zn2+ content in the range of 0 ≤ x ≤ 2.0, the discussed NPs can sequentially acquire valuable properties enabling magnetic resonance imaging, near-infrared (NIR) photothermal effects, NIR photocatalytic and photoelectric effects, depending on the variation of substitution position of the Zn2+ in the magnetite structure and the emergence of a ZnO/ZnFe2 O4 heterostructure at high doping concentrations. The presented work demonstrates and explainsa facile route for the synthesis and modulation of multifunctional nanomaterials with manifold roles in disease diagnostics and therapy, and provides helpful guidance in designing divalent transition metal ion-doped nanomaterials.

IGF1 receptor-targeted black TiO2 nanoprobes for MRI-guided synergetic photothermal-chemotherapy in drug resistant pancreatic tumor.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO2-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO2-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.

Mixed Metal Metal-Organic Frameworks Derived Carbon Supporting ZnFe2O4/C for High-Performance Magnetic Particle Imaging.

Recently, magnetic particle imaging (MPI) has shown diverse biomedical applications such as cell tracking, lung perfusion, image-guided hyperthermia, and so forth. However, the currently reported MPI agents cannot achieve the possible theoretical detection limit of MPI (20 nM). A previous theoretical study has shown that the MPI performance of superparamagnetic iron oxide nanoparticles (SPIONs) can be enhanced by carbon supporting and metal doping. In the current study, a series of mixed metal metal-organic framework-derived carbon supporting SPIONs were synthesized by pyrolysis. Among the synthesized SPIONs, the MPI signal intensity of ZnFe2O4/C@PDA was found to be 4.7 times higher than the commercial MPI contrast (Vivotrax) having the same Fe concentration. ZnFe2O4/C@PDA also showed the highest MPI intensity in tumor-bearing-mice among all tested samples. Furthermore, they were found highly biocompatible and showed linear cell quantification. This work can open new avenues for the design and development of novel and high-performance MPI agents.

Intelligent Pore Switch of Hollow Mesoporous Organosilica Nanoparticles for High Contrast Magnetic Resonance Imaging and Tumor-Specific Chemotherapy.

Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.

Fluorescent carbon dots with excellent moisture retention capability for moisturizing lipstick.

Long-lasting moisture retention is a huge challenge to humectants, and effective methods or additives for promote these functions are limited, especially nano-additives. Carbon dots (CDs) have attracted increasing research interest due to its ultra-small size, excellent optical properties and low toxicity, etc. However, most of researches have been focused on the photoexcited CDs and its subsequent photophysical and chemical processes, such as photoluminescence, photodynamic, photothermal and photocatalytic behavior. The intrinsic chemo-physical properties of the pristine CDs are not fully explored. Here, we report an excellent moisture retention capability of a new carmine cochineal-derived CDs (Car-CDs) for the first time. The relationship between the structure of Car-CDs and its moisture retention capability is revealed. More interestingly, the effective applications of Car-CDs in moisturizing lipstick are demonstrated. This work expands the research and application of CDs into a broad, new area, potentially in skin care.

Research progress and mechanism of nanomaterials-mediated in-situ remediation of cadmium-contaminated soil: A critical review.

Cadmium contamination of soil is a global issue and in-situ remediation technology as a promising mitigation strategy has attracted more and more attention. Many nanomaterials have been applied for the in-situ remediation of cadmium-contaminated soil due to their excellent properties of the nano-scale size effect. In this work, recent research progress of various nanomaterials, including carbon nanomaterials, metal-based nanomaterials and nano mineral materials, in the removal of cadmium and in-situ remediation of cadmium-contaminated soil were systematically discussed. Additional emphases were particularly laid on both laboratory and field restoration effects. Moreover, the factors which can affect the stability of cadmium, main interaction mechanisms between nanomaterials and cadmium in the soil, and potential future research direction were also provided. Therefore, it is believed that this work will ultimately contribute to the myriad of environmental cleanup advances, and further improve human health and sustainable development.

A prognostic five long-noncoding RNA signature for patients with rectal cancer.

This study aimed to identify prognostic long noncoding RNAs (lncRNAs) signature for predicting the prognosis of patients with rectal cancer. LncRNA-sequencing data and clinicopathological data of patients with rectal cancer were retrieved from The Cancer Genome Atlas database. Univariate and multivariate Cox proportional hazards regression analysis, the least absolute shrinkage, and selection operator analysis and the Kaplan-Meier curve method were employed to identify prognostic lncRNAs and construct multi-lncRNA signature. Finally, five lncRNAs (AC079789.1, AC106900.2, AL121987.1, AP004609.1, and LINC02163) were identified to construct a five-lncRNA signature. According to the five-lncRNA signature, patients with rectal cancer were divided into a high-risk group and low-risk group. Patients with rectal cancer had significantly poorer overall survival in the high-risk group than in the low-risk group. We used a time-dependent receiver operating characteristic curve to assess the power of the five-lncRNA signature by calculating the area under the curve (AUC). The AUCs for predicting 3-year survival and 5-year survival were 0.742 and 0.935, respectively, which indicated a good performance of the five-lncRNA signature. The five-lncRNA signature was independently associated with the prognosis of patients with rectal cancer through using univariate and multivariate Cox regression analysis. The biological function of the five lncRNAs was enriched in some cancer-related biological processes and pathways by performing functional enrichment analysis of their correlated protein-coding genes. In conclusion, we developed a five-lncRNA signature as a potential indicator for rectal cancer.

Ten-Gram-Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis.

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T1 contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten-gram-scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd-salicylate nanoparticles, GdSalNPs-rBSA) with high r1 value of 19.51 mm-1 s-1 and very low r2 /r1 ratio of 1.21 (B0 = 1.5 T) for high-contrast T1 -weighted MRI of tumors. The GdSalNPs-rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t1/2 = 6.13 h), almost no Gd3+ release, and excellent biosafety. Moreover, the GdSalNPs-rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal-to-noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.

A Hybrid Organo-Nanotheranostic Platform of Superlative Biocompatibility for Near-Infrared-Triggered Fluorescence Imaging and Synergistically Enhanced Ablation of Tumors.

The quest for an all-organic nanosystem with negligible cytotoxicity and remarkable in vivo tumor theranostic capability is inescapably unending. Hitherto, the landscape of available photothermal agents is dominated by metal-based nanoparticles (NPs) with attendant in vivo negatives. Here, an all-organic-composed theranostic nanosystem with outstanding biocompatibility for fluorescence image-guided tumor photothermal therapy, and as a potential alternative to metal-based photothermal agents is developed. This is rationally achieved by compartmentalizing indocyanine green (ICG) in glycol chitosan (GC)-polypyrrole (PP) nanocarrier to form hybrid ICG@GC-PP NPs (≈65 nm). The compartmentalization strategy, alongside the high photothermal conversion ability of PP jointly enhances the low photostability of free ICG. Advantageously, ICG@GC-PP is endowed with an impeccable in vivo performance by the well-known biocompatibility track records of its individual tri organo-components (GC, PP, and ICG). As a proof of concept, ICG@GC-PP NPs enables a sufficiently prolonged tumor diagnosis by fluorescence imaging up to 20 h post-injection. Furthermore, owing to the complementary heating performances of PP and ICG, ICG@GC-PP NPs-treated mice by one-time near-infrared irradiation exhibit total tumor regression within 14 days post-treatment. Therefore, leveraging the underlying benefits of this study will help to guide the development of new all-organic biocompatible systems in synergism, for safer tumor theranostics.

Nanoparticle-Based Wound Dressing: Recent Progress in the Detection and Therapy of Bacterial Infections.

Bacterial infections in wounds often delay the healing process, and may seriously threaten human life. It is urgent to develop wound dressings to effectively detect and treat bacterial infections. Nanoparticles have been extensively used in wound dressings because of their specific properties. This review highlights the recent progress on nanoparticle-based wound dressings for bacterial detection and therapy. Specifically, nanoparticles have been applied as intrinsic antibacterial agents or drug delivery vehicles to treat bacteria in wounds. Moreover, nanoparticles with photothermal or photodynamic property have also been explored to endow wound dressings with significant optical properties to further enhance their bactericidal effect. More interestingly, nanoparticle-based smart dressings have been recently explored for bacteria detection and treatment, which enables an accurate assessment of bacterial infection and a more precise control of on-demand therapy.

Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.

Sonothrombolysis with microbubbles can enhance the dissolution of thrombus through the cavitation effect of microbubbles under ultrasound irradiation. However, the detailed mechanism of thrombolysis with microscaled or nanoscaled bubbles is still not so clear. This study compared the thrombolytic capacity of cRGD-targeted or nontargeted bubbles with different particle sizes combined with urokinase (UK). The size of the microscaled bubbles (Mbs or Mbs-cRGD) was mostly approximately 3 µm, while the nanoscaled bubbles (Nbs or Nbs-cRGD) were mainly around 220 nm. In vitro testing was performed on an extracorporeal circulation device that mimics human vascular thromboembolism. The rabbit clots in Mbs with UK groups showed peripheral worm-like dissolution, while the clots in Nbs with UK groups showed internal fissure-like collapse. In addition, the thrombolysis rate of Nbs-cRGD with the UK group was the highest. Furthermore, the scanning electron microscopic images showed that the fibrin network was the most severely damaged by the Nbs-cRGD, and most of the fibrin strands were dissolved. Especially, the Nbs-cRGD can penetrate much deeper than Mbs-cRGD into the thrombus and loosen the fibrin network. Taken together, benefiting from the specific identification and deep penetration to thrombus, our developed novel targeted Nbs may have broad application prospects in the clinic.

Microfluidic applications on circulating tumor cell isolation and biomimicking of cancer metastasis.

The prognosis of malignant tumors is challenged by insufficient means to effectively detect tumors at early stage. Liquid biopsy using circulating tumor cells (CTCs) as biomarkers demonstrates a promising solution to tackle the challenge, because CTCs play a critical role in cancer metastatic process via intravasation, circulation, extravasation, and formation of secondary tumor. However, the effectiveness of the solution is compromised by rarity, heterogeneity, and vulnerability associated with CTCs. Among a plethora of novel approaches for CTC isolation and enrichment, microfluidics leads to isolation and detection of CTCs in a cost-effective and operation-friendly way. Development of microfluidics also makes it feasible to model the cancer metastasis in vitro using a microfluidic system to mimick the in vivo microenvironment, thereby enabling analysis and monitor of tumor metastasis. This paper aims to review the latest advances for exploring the dual-roles microfluidics has played in early cancer diagnosis via CTC isolation and investigating the role of CTCs in cancer metastasis; the merits and drawbacks for dominating microfluidics-based CTC isolation methods are discussed; biomimicking cancer metastasis using microfluidics are presented with example applications on modelling of tumor microenvironment, tumor cell dissemination, tumor migration, and tumor angiogenesis. The future perspectives and challenges are discussed.

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides.

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l-α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application. The liposomal formulations based on cobalt and iron bis(dicarbollide)-based lipids were found to be nontoxic against both human breast normal epithelial cells MCF-10A and human breast cancer cells MCF-7.

The design and biomedical applications of self-assembled two-dimensional organic biomaterials.

The design and applications of some inorganic two-dimensional (2D) nanomaterials such as graphene, graphyne, and borophene have been widely studied in recent years. Meanwhile, it has been noticed that self-assembling two-dimensional organic biomaterials (2DOBMs) including films, membranes, nanosheets, nanoribbons, grids, arrays, and lattices based on various biomolecules also exhibited promising structures, functions, and applications. The in-depth studies on the self-assembly formation, structural and functional tailoring of 2DOBMs open new avenues for the next generation of novel nanomaterials with adjustable structure and functions, which would further promote the applications of 2DOBMs in materials science, nanodevices, energy and environmental science, biomedicine, tissue engineering, and analytical science. In this review, we summarize important information on the basic principles to fabricate self-assembling 2DOBMs based on peptides, proteins, DNA, RNA, viruses, and other biopolymers. The potential strategies and techniques for tailoring and controlling the structures and functions of 2DOBMs are presented and discussed further. The function-specific biomedical applications of 2DOBMs in biosensors, biomimetic mineralization, cell growth, drug/gene delivery, and bioimaging are also highlighted.