Interleukin-17A Promotes Airway Remodeling in Chronic Obstructive Pulmonary Disease by Activating C-X-C Motif Chemokine Ligand 12 Secreted by Lung Fibroblasts.

Background: The interactions between fibroblasts and bronchial epithelial cells play important roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin (IL)-17A triggers the activation of fibroblasts and secretion of inflammatory mediators, which promotes epithelial mesenchymal transition (EMT) in bronchial epithelial cells. Fibroblasts secrete C-X-C motif chemokine ligand 12 (CXCL12), which specifically binds to its receptor, C-X-C motif chemokine receptor 4 (CXCR4) to mediate inflammatory responses. This study aims to investigate IL-17A- and CXCL12-induced airway remodeling. Methods: Primary lung fibroblasts were isolated from human and murine lung tissue for the in vitro experiments, and a mouse model of cigarette smoke (CS)-induced COPD was established for the in vivo experiments. The results were analyzed using one-way ANOVA and Tukey's test or Bonferroni's test for post-hoc test. A p-value < 0.05 was considered statistically significant. Results: Through in vitro experiments, we found that IL-17A-activated primary lung fibroblasts secreted CXCL12 and stimulated EMT in bronchial epithelial cells. However, these effects could be blocked by neutralizing IL-17A or CXCL12. In vivo, an anti-IL-17A antibody or a CXCR4 antagonist (AMD3100) could reverse the degree of EMT in lungs of the COPD mouse model. The IL-17A-induced EMT and increased CXCL12 expression occurred via extracellular signal-regulated kinase (ERK)/phosphorylated (p-)ERK pathways. Conclusion: This study showed that exposure of mice to CS and IL-17A stimulation upregulated CXCL12 expression and induced EMT by activating the ERK signaling pathway. These data offer a novel perspective regarding the molecular mechanism of CXCL12/CXCR4 signaling in IL-17A-induced EMT related to airway remodeling.

Ex vivo near-infrared targeted imaging of human bladder carcinoma by ICG-anti-CD47.

Objective: The low detection rate of early-stage and small tumors remains a clinical challenge. A solution to this unmet need is urgently warranted for the accurate diagnosis and treatment of bladder cancer (BC). This study aimed to evaluate the feasibility of CD47 as a target for optical molecular imaging of human BC and conduct preliminary ex vivo imaging experiments. Method: Using indocyanine green (ICG) and a CD47 antibody (anti-CD47), we synthesized a new targeted fluorescent probe ICG-anti-CD47. A total of 25 patients undergoing radical cystectomy were prospectively included in ex vivo imaging experiments. Following surgery, the freshly isolated bladder specimens were incubated with ICG-anti-CD47, and images were captured under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with those of CD47-targeted NIR molecular imaging. Results: Based on the ex vivo imaging experiments, 23 and 2 patients were pathologically diagnosed with bladder urothelial carcinoma and bladder squamous cell carcinoma, respectively. There were no adverse effects of ICG-anti-CD47 on the histological structure of the tumor and normal uroepithelium. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which markedly improved tumor visualization. Conclusion: Anti-CD47-targeted NIR molecular imaging may be a feasible and powerful strategy for the accurate diagnosis of BC. Nevertheless, larger-scale randomized trials are warranted to verify the present findings.

Specific and Long-Term Luminescent Monitoring of Hydrogen Peroxide in Tumor Metastasis.

Luminescent monitoring of endogenous hydrogen peroxide (H2 O2 ) in tumors is conducive to understanding metastasis and developing novel therapeutics. The clinical transformation is obstructed by the limited light penetration depth, toxicity of nano-probes, and lack of long-term monitoring modes of up to days or months. New monitoring modes are introduced via specific probes and implantable devices, which can achieve real-time monitoring with a readout frequency of 0.01 s or long-term monitoring for months to years. Near-infrared dye-sensitized upconversion nanoparticles (UCNPs) are fabricated as the luminescent probes, and the specificity to reactive oxygen species is subtly regulated by the self-assembled monolayers on the surfaces of UCNPs. Combined with the passive implanted system, a 20-day monitoring of H2 O2 in the rat model of ovarian cancer with peritoneal metastasis is achieved, in which the limited light penetration depth and toxicity of nano-probes are circumvented. The developed monitoring modes show great potential in accelerating the clinical transformation of nano-probes and biochemical detection methods.

Responsive Accumulation of Nanohybrids to Boost NIR-Phototheranostics for Specific Tumor Imaging and Glutathione Depletion-Enhanced Synergistic Therapy.

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH-responsive i-motif DNA-mediated strategy to tailor the programmable behaviors of erbium-based rare-earth nanoparticles (ErNPs) decorated copper doped metal-organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i-motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near-infrared (NIR) photon-activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications.

Vitamin B12 deficiency may play an etiological role in atrophic glossitis and its grading: A clinical case-control study.

BACKGROUND: Existing studies have reported the significant association between atrophic glossitis (AG) and hematinic deficiencies, including iron, folate and vitamin B12 deficiency. However, these findings were inconsistent. AG can be graded as partial or complete atrophy. It is still unclear whether hematinic deficiencies are associated with the grading of AG. METHODS: 236 AG patients and 208 sex- and age-matched healthy controls were enrolled in this study. Hematological tests including complete blood count, and serum levels of folate, ferritin and vitamin B12 were performed. The AG group was divided into those with partial AG and those with complete AG according to the extent of papillary atrophy. Statistical analysis was performed to assess whether hematinic deficiencies are risk factors for AG and its grading. RESULTS: Compared with the healthy controls, AG patients had significantly higher frequencies of vitamin B12 deficiency (68.22%), ferritin deficiency (13.98%) and anemia (21.61%). The differences in hematinic deficiencies and anemia between AG patients and healthy controls changed according to gender and age. The frequencies of serum vitamin B12 deficiency and anemia in the complete AG subgroup were significantly higher than those in the partial AG subgroup. Logistic regression analysis revealed that vitamin B12 deficiency and anemia were significantly correlated with AG and its grading. The AG patients with vitamin B12 deficiency responded well to supplement therapy. CONCLUSION: AG could be an important clinical indicator for potential vitamin B12 deficiency, especially when the degree of tongue atrophy more than 50% and complete atrophy. Vitamin B12 deficiency might play an etiological role in the development of AG.

A bimodal type of AgPd Plasmonic Blackbody Nanozyme with boosted catalytic efficacy and synergized photothermal therapy for efficacious tumor treatment in the second biological window.

Nanozymes are promising for precise cancer treatment, but are typically limited in terms of the low catalytic efficiency and the complexity in tumor microenvironment (TME). Herein, we describe a bimodal type of AgPd plasmonic blackbody (AgPd PB) nanozyme of compact sizes (< 30 nm), which presents not only boosted enzyme efficacy but also efficient photothermal therapy (PTT) for synergized therapy through tissue-penetrating light in the second biological window (1000-1700 nm). The synthesized hyperbranched AgPd PB nanozymes possess intense and broadband localized surface plasmonic resonance absorption of 400-1300 nm, entailing prominent photothermal efficiency (η = 45.1% at 1064 nm) for PTT. Importantly, PTT was found to significantly boost the nanozyme efficacy of both catalase (CAT) and peroxidase (POD) processes, which correspondingly decompose H2O2 to into O2 to relieve tumor hypoxia, and activate H2O2 to generate oxidative •OH radical. While the generated •OH was found to be able to minimize heat shock proteins (HSPs), which plays a vital role to counterbalance PTT effect both in vitro and in vivo. As compared to control ground without treatment, the synergized nanozyme and PTT activities resulted in about 7-fold reduction of tumor volume, thus elevating the survival rate from 0 to 80% at 30 days posttreatment. Besides the synergistic therapy, the AgPd PB nanozyme were shown to own fluorescence, computed tomography (CT), and photoacoustic (PA) imaging abilities, thus having implications for uses in imaging-guided precise cancer therapy. This study provides a paradigm of TME responsive theranostics under NIR-II light irradiation.

Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.

Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c-MYC). Additionally, KPNA2 knockdown regulated CSC-related gene expression in radioresistant cells. Next-generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2-mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1-STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.

A Class of Biocompatible Dye-Protein Complex Optical Nanoprobes.

Molecular organic dyes are classic fluorescent nanoprobes finding tremendous uses in biological and life sciences. Yet, they suffer from low brightness, poor photostability, and lack of functional groups for bioconjugation. Here, we describe a class of biocompatible dye-protein optical nanoprobes, which show long-time photostability, superbrightness, and enriched functional groups. These nanoprobes utilize apoferritin (an intracellular protein for iron stores and release) to encase appropriate molecular organic dyes to produce on-demand fluorescence in aqueous solution. A pH-driven dissociation-reconstitution process of apoferritin subunits allows substantial incorporation of hydrophilic (aggregation caused quenching, ACQ) or hydrophobic (aggregation induced enhancement, AIE) dye molecules into the protein nanocavity (8 nm), producing monodispersed dye-apoferritin nanoparticles (apo-dye-NPs, ∼12 nm). As compared with single dye monomer, single apo-dye-NPs possess hundreds of times larger molar extinction coefficient and 2 orders of magnitude higher absolute luminescence quantum yield (up to 45-fold), multiplying fluorescence brightness up to 2778-fold. We show that varying the type of incorporated dyes entails a precise control over nanoprobe emission profile tunable in a broad spectral range of 370-1300 nm. Mechanical investigations indicate that the diversified microstructures of nanocavity inner surface are able to conform ACQ dyes at reasonable space interval while providing protein-guided-stacking for AIE dyes, thus enhancing fluorescence quantum yield through confining intermolecular quenching and intramolecular rotation. Moreover, apo-dye-NPs are able to emit stable fluorescence (over 13 min) without quenching in confocal imaging of HepG2 cancer cell under ultrahigh laser irradiance (1.3 × 106 W/cm2). These superb properties make them suitable, as demonstrated in this work, for long-term super-resolved structured illumination microscopic cell imaging (spatial resolution, 117 nm) over 48 h, near-infrared (NIR) fluorescence angiography imaging of whole-body blood vessels (spatial resolution, 380 µm), and NIR photoacoustic imaging of liver in vivo.

Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization.

BACKGROUND: In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall ß-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. RESULTS: Our ultrasmall ß-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS. CONCLUSION: These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.

Multimode Imaging-Guided Photothermal/Chemodynamic Synergistic Therapy Nanoagent with a Tumor Microenvironment Responded Effect.

The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoOx NPs (DCDMs) with a flower-like structure fabricated by coating uniformly sized down-conversion nanoparticles (DCNPs) with dendritic mesoporous silica (DMSN) and then loading the ultrasmall oxygen-deficient molybdenum oxide nanoparticles (MoOx NPs) inside through an electrostatic interaction. Owing to the doping of Nd ions, when excited by an 808 nm laser, DCNPs emit bright NIR-II emissions (1060 and 1300 nm), which have characteristic high spatial resolution and deep tissue penetration. In terms of treatment, MoOx NPs could be specifically activated by excessive hydrogen peroxide (H2O2) in the tumor microenvironment, thus generating 1O2 via the Russell mechanism. In addition, the excessive glutathione (GSH) in the tumor cells could be depleted through the Mo-mediated redox reaction, thus effectively decreasing the antioxidant capacity of tumor cells. Importantly, the excellent photothermal properties (photothermal conversion efficiency of 51.5% under an 808 nm laser) synergistically accelerate the generation of 1O2. This cyclic redox reaction of molybdenum indeed ensured the high efficacy of tumor-specific therapy, leaving the normal tissues unharmed. MoOx NPs could also efficiently catalyze tumor endogenous H2O2 into a considerable amount of O2 in an acidic tumor microenvironment, thus relieving hypoxia in tumor tissues. Moreover, the computed tomography (CT) and T1-weighted magnetic resonance imaging (MRI) effect from Gd3+ and Y3+ ions make DCNPs act as a hybrid imaging agent, allowing comprehensive analysis of tumor lesions. Both in vitro and in vivo experiments validate that such an "all-in-one" nanoplatform possesses desirable anticancer abilities under single laser source irradiation, benefiting from the NIR-II fluorescence/CT/MR multimodal imaging-guided photothermal/chemodynamic synergistic therapy. Overall, our strategy paves the way to explore other noninvasive cancer phototheranostics.

All-in-One Theranostic Nanomedicine with Ultrabright Second Near-Infrared Emission for Tumor-Modulated Bioimaging and Chemodynamic/Photodynamic Therapy.

Reactive oxygen species (ROS)-based therapeutic modalities including chemodynamic therapy (CDT) and photodynamic therapy (PDT) hold great promise for conquering malignant tumors. However, these two methods tend to be restricted by the overexpressed glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Here, we develop biodegradable copper/manganese silicate nanosphere (CMSN)-coated lanthanide-doped nanoparticles (LDNPs) for trimodal imaging-guided CDT/PDT synergistic therapy. The tridoped Yb3+/Er3+/Tm3+ in the ultrasmall core and the optimal Yb3+/Ce3+ doping in the shell enable the ultrabright dual-mode upconversion (UC) and downconversion (DC) emissions of LDNPs under near-infrared (NIR) laser excitation. The luminescence in the second near-infrared (NIR-II, 1000-1700 nm) window offers deep-tissue penetration, high spatial resolution, and reduced autofluorescence when used for optical imaging. Significantly, the CMSNs are capable of relieving the hypoxic TME through decomposing H2O2 to produce O2, which can react with the sample to generate 1O2 upon excitation of UC photons (PDT). The GSH-triggered degradation of CMSNs results in the release of Fenton-like Mn2+ and Cu+ ions for •OH generation (CDT); simultaneously, the released Mn2+ ions couple with NIR-II luminescence imaging, computed tomography (CT) imaging, and magnetic resonance (MR) imaging of LDNPs, performing a TME-amplified trimodal effect. In such a nanomedicine, the TME modulation, bimetallic silicate photosensitizer, Fenton-like nanocatalyst, and NIR-II/MR/CT contrast agent were achieved "one for all", thereby realizing highly efficient tumor theranostics.

Detecting Ferric Iron by Microalgal Residue-Derived Fluorescent Nanosensor with an Advanced Kinetic Model.

Biomass-derived carbon quantum dots (CQDs) are attractive to serve as fluorescent nanosensors owing to their superior environmental compatibility and biocompatibility. However, the detection range has been limited, only in partial agreement with the experimental data. Thus, an advanced kinetic model for quantifying the fluorescence quenching over a wide range is on demand. Here, we describe a nanosensor for Fe(Ⅲ) detection in real waters, which is developed via microalgal residue-derived CQDs with an advanced kinetic model. The multiple-order kinetic model is established to resolve the incoherence of previous models and unveil the entire quenching kinetics. The results show that the detection range of Fe(Ⅲ) can reach up to 10 mM in the high detection end. The newly obtained kinetic model exhibits satisfactory fittings, clearly elucidating a dynamic quenching mechanism. This work provides a new insight into CQDs-based detection of heavy metals in real water samples by establishing an innovative multiple-order kinetic model.

Prussian blue-coated lanthanide-doped core/shell/shell nanocrystals for NIR-II image-guided photothermal therapy.

Lanthanide-doped nanoparticles have long been stereotyped for optical luminescence bioimaging. However, they are known to be unable to produce therapeutic abilities. Here, we describe a lanthanide-based theranostic agent, namely, prussian blue (PB)-coated NaErF4@NaYF4@NaNdF4 core/shell/shell nanocrystals encapsulated in a phospholipid PEG micelle (PEG-CSS@PB), which showed switched imaging and hyperthermia abilities under distinct near infrared (NIR) light activation. The erbium (Er3+)-enriched inner core nanocrystals (NaErF4) enabled the emission of tissue-penetrating luminescence (1525 nm) in the second biological window (NIR-II, 1000-1700 nm), which endowed high-resolution optical imaging of the blood vessels and tumors under ∼980 nm excitation. High neodymium (Nd3+) concentrations in the epitaxial outer NaNdF4 shell introduced maximum cross relaxation processes that converted the absorbed NIR light (∼808 nm) into heat at high efficiencies, thus providing abilities for photothermal therapy (PTT). Importantly, the coated Prussian blue (PB) increased light absorption by about 10-fold compared to the composite free of PB, thus entailing a high light-to-heat conversion efficiency of ∼50.5%. This commensurated with that of well-established gold nanorods. As a result, the PEG-CSS@PB nanoparticles with MTT-determined low toxicities resulted in ∼80% death of HeLa cells at a dose of 600 µg mL-1 under 808 nm laser irradiance (1 W cm-2) for 10 min. Moreover, utilizing the same light dose, a single PTT treatment in tumor-bearing BALB/c mice shrunk the tumor size by ∼12-fold compared to the tumors without treatment. Our results, here, constituted a solid step forward to entitle lanthanide-based nanoparticles as theranostic agents in nanomedicine studies.

A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-ß-Cyclodextrin.

Lanthanide-doped upconverting nanoparticles (UCNPs) are promising for applications as wide as biosensing, bioimaging, controlled drug release, and cancer therapy. These applications require surface engineering of as-prepared nanocrystals, commonly coated with hydrophobic ligand of oleic acid, to enable an aqueous dispersion. However, literature-reported approaches often require a long time and/or multiple step treatment, along with several fold upconversion luminescence (UCL) intensity decrease. Here, we describe a strategy allowing oleate-capped UCNPs to become water-soluble and open-modified, with almost undiminished UCL, through ultrasonication of minutes. The prompt phase transfer was enabled by oleate-mediated supramolecular self-assembly of amino modified ß-cyclodextrin (amino-ß-CD) onto UCNPs surface. We showed that this method is valid for a wide range of UCNPs with quite different sizes (6-400 nm), various dopant types (Er, Tm, and Ho), and hierarchical structures (core, core-shell). Importantly, the amino group of amino-ß-CD on the surface of treated UCNPs provide possibilities to introduce entities for biotargeting or functionalization, as exemplified here, a carboxylic-containing near infrared dye (Cy 7.5) that sensitizes UCNPs to enhance their UCL by ~4,820 fold when excited at ~808 nm. The described method has implications for all types of oleate-capped inorganic nanocrystals, facilitating their myriad bioapplications.

Recent Progress in Upconversion Photodynamic Therapy.

Photodynamic therapy (PDT) is a minimally invasive cancer modality that combines a photosensitizer (PS), light, and oxygen. Introduction of new nanotechnologies holds potential to improve PDT performance. Upconversion nanoparticles (UCNPs) offer potentially advantageous benefits for PDT, attributed to their distinct photon upconverting feature. The ability to convert near-infrared (NIR) light into visible or even ultraviolet light via UCNPs allows for the activation of nearby PS agents to produce singlet oxygen, as most PS agents absorb visible and ultraviolet light. The use of a longer NIR wavelength permits light to penetrate deeper into tissue, and thus PDT of a deeper tissue can be effectively achieved with the incorporation of UCNPs. Recent progress in UCNP development has generated the possibility to employ a wide variety of NIR excitation sources in PDT. Use of UCNPs enables concurrent strategies for loading, targeting, and controlling the release of additional drugs. In this review article, recent progress in the development of UCNPs for PDT applications is summarized.

Stable ICG-loaded upconversion nanoparticles: silica core/shell theranostic nanoplatform for dual-modal upconversion and photoacoustic imaging together with photothermal therapy.

We report here the design and multiple functions of a new hierarchical nanotheronostic platform consisting of an upconversion nanoparticle (UCNP) core: shell with an additional mesoporous silica (mSiO2) matrix load shell containing sealed, high concentration of ICG molecules. We demonstrate that this UCNP@mSiO2-ICG nanoplatform can perform the following multiple functions under NIR excitation at 800 nm: 1) Light harvesting by the UCNP shell containing Nd and subsequent energy transfer to Er in the Core to produce efficient green and red upconversion luminescence for optical imaging; 2) Efficient nonradiative relaxation and local heating produced by concentration quenching in aggregated ICG imbedded in the mesopourous silica shell to enable both photoacoustic imaging and photothermal therapy. Compared to pure ICG, sealing of mesoporous silica platforms prevents the leak-out and improves the stability of ICG by protecting from rapid hydrolysis. Under 800 nm laser excitation, we performed both optical and photoacoustic (PA) imaging in vitro and in vivo. Our results demonstrated that UCNP@mSiO2-ICG with sealed structures could be systemically delivered to brain vessels, with a long circulation time. In addition, these nanoplatforms were capable of producing strong hyperthermia efforts to kill cancer cells and hela cells under 800 nm laser irradiation.

Dopamine-mediated photothermal theranostics combined with up-conversion platform under near infrared light.

An organic-inorganic hybrid core-shell nanostructure, based on mesoporous silica coated upconversion core-shell nanoparticles (NaGdF4:Yb,Er@NaGdF4:Yb@mSiO2-Dopa abbreviated here as UCNP@mSiO2-Dopa) that stably incorporates dopamine (Dopa) in the silica layer was introduced as a theranostic nanoplatform for optical imaging guided photothermal therapy (PTT) using NIR excitation. Silica-attaching polyethylenimine make the Dopa transforms into an active form (transferred Dopa) that strongly absorbs light under single 980 nm irradiation. We show that the activated UCNP@mSiO2-Dopa nanoplatform is able to produce a pronounced photothermal effect, that elevates water temperature from room temperature to 41.8 °C within 2 minutes, while concurrently emitting strong upconverted luminescence (UCL) for visualized guidance under 980 nm laser. In addition, we demonstrate the application of the same UCNP@mSiO2-Dopa nanoplatform for magnetic resonance imaging (MRI) and x-ray computed tomography (CT) enabled by the gadolinium (Gd) element contained in the UCNP. Importantly, the in vitro and in vivo anti-cancer therapeutic effects have been shown efficacious, implying the use of the described nanoplatform as an effective multi-modal imaging enabled PTT agent. Results from the in vivo biodistribution of UCNPs@mSiO2, cellular live/dead assay, and histologic analysis of main organs of treated mice, reveal that the UCNP@mSiO2-Dopa agents are bio-compatible with low toxicity.

Hepatocyte growth factor (HGF) optimizes oral traumatic ulcer healing of mice by reducing inflammation.

OBJECTIVE: To evaluate the influence of overexpression HGF on the healing of traumatic ulcer of oral mucosa of mice. MATERIAL AND METHODS: Mice were divided into two groups: wild type C57BL6(WT) and HGF high expression transgenic (HGF-Tg) mice. Traumatic ulcer of all mice were made by number 15 scalpel blade. Mice were sacrificed after 5days and the inflammation score and expression of TNFα, IFNγ, c-Met, apoptosis (TUNEL) and 40 serum inflammation cytokines were estimated. RESULTS: HGF-Tg mice presented a lower inflammation score (p=0.011), Serum TNFα expression in HGF-Tg ulcers is 1.3 times than WT ulcer and the difference is statistical significance (t test, p=0.003). Serum c-Met protein in HGF-Tg mice were significantly higher than WT mice (t test, p=0.004). No statistical difference was observed in the serum IFNγ between WT ulcer and HGF-Tg ulcer (t test, p=0.268). TNFα positive cytoplasm expression cells in connective tissue of HGF-Tg mice is significantly lower than that of WT group (t test, p=0.029). C-Met positive cytoplasm expression cells in both epithelium and connective tissue of HGF-Tg group is significantly higher than that of WT group (t test, p=0.040, p=0.000). Samples in HGF-Tg group showed a lower number of positive cells of epithelium TUNEL staining compared with that in the WT group (t test, p=0.035). CONCLUSIONS: HGF exhibited anti-inflammatory potential in oral traumatic ulcer through the reduction of epithelial apoptosis, connective tissue TNFα expression and induction of c-Met expression.

Synthesis and Optimization of MoS2@Fe3O4-ICG/Pt(IV) Nanoflowers for MR/IR/PA Bioimaging and Combined PTT/PDT/Chemotherapy Triggered by 808 nm Laser.

Elaborately designed biocompatible nanoplatforms simultaneously achieving multimodal bioimaging and therapeutic functions are highly desirable for modern biomedical applications. Herein, uniform MoS2 nanoflowers with a broad size range of 80-180 nm have been synthesized through a facile, controllable, and scalable hydrothermal method. The strong absorbance of MoS2 nanoflowers at 808 nm imparts them with high efficiency and stability of photothermal conversion. Then a novel multifunctional composite of MoS2@Fe3O4-ICG/Pt(IV) (labeled as Mo@Fe-ICG/Pt) is designed by covalently grafting Fe3O4 nanoparticles with polyethylenimine (PEI) functionalized MoS2, and then loading indocyanine green molecules (ICG, photosensitizers) and platinum (IV) prodrugs (labeled as Pt(IV) prodrugs) on the surface of MoS2@Fe3O4. The resulting Mo@Fe-ICG/Pt nanocomposites can achieve excellent magnetic resonance/infrared thermal/photoacoustic trimodal biomaging as well as remarkably enhanced antitumor efficacy of combined photothermal therapy, photodynamic therapy, and chemotherapy triggered by a single 808 nm NIR laser, thus leading to an ideal nanoplatform for cancer diagnosis and treatment in future.

Surfactant-stripped naphthalocyanines for multimodal tumor theranostics with upconversion guidance cream.

Surfactant-stripped, nanoformulated naphthalocyanines (nanonaps) can be formed with Pluronic F127 and low temperature membrane processing, resulting in dispersed frozen micelles with extreme contrast in the near infrared region. Here, we demonstrate that nanonaps can be used for multifunctional cancer theranostics. This includes lymphatic mapping and whole tumor photoacoustic imaging following intradermal or intravenous injection in rodents. Without further modification, pre-formed nanonaps were used for positron emission tomography and passively accumulated in subcutaneous murine tumors. Because the nanonaps used absorb light beyond the visible range, a topical upconversion skin cream was developed for anti-tumor photothermal therapy with laser placement that can be guided by the naked eye.