Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel.

BACKGROUND: Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always "on", and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor. RESULTS: In this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light. CONCLUSIONS: This work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.

In vivo visualization of tumor-associated macrophages re-education by photoacoustic/fluorescence dual-modal imaging with a metal-organic frames-based caspase-1 nanoreporter.

Tumor-associated macrophages (TAMs) are vital in the tumor microenvironment, contributing to immunosuppression and therapy tolerance. Despite their importance, the precise re-education of TAMs in vivo continues to present a formidable challenge. Moreover, the lack of real-time and efficient methods to comprehend the spatiotemporal kinetics of TAMs repolarization remains a significant hurdle, severely hampering the accurate assessment of treatment efficacy and prognosis. Herein, we designed a metal-organic frameworks (MOFs) based Caspase-1 nanoreporter (MCNR) that can deliver a TLR7/8 agonist to the TAMs and track time-sensitive Caspase-1 activity as a direct method to monitor the initiation of immune reprogramming. This nanosystem exhibits excellent TAMs targeting ability, enhanced tumor accumulation, and stimuli-responsive behavior. By inducing the reprogramming of TAMs, they were able to enhance T-cell infiltration in tumor tissue, resulting in inhibited tumor growth and improved survival in mice model. Moreover, MCNR also serves as an activatable photoacoustic and fluorescent dual-mode imaging agent through Caspase-1-mediated specific enzyme digestion. This feature enables non-invasive and real-time antitumor immune activation monitoring. Overall, our findings indicate that MCNR has the potential to be a valuable tool for tumor immune microenvironment remodeling and noninvasive quantitative detection and real-time monitoring of TAMs repolarization to immunotherapy in the early stage.

Tumor Microenvironment Activated Photoacoustic-Fluorescence Bimodal Nanoprobe for Precise Chemo-immunotherapy and Immune Response Tracing of Glioblastoma.

Synergistic therapy strategy and prognostic monitoring of glioblastoma's immune response to treatment are crucial to optimize patient care and advance clinical outcomes. However, current systemic temozolomide (TMZ) chemotherapy and imaging methods for in vivo tracing of immune responses are inadequate. Herein, we report an all-in-one theranostic nanoprobe (PEG/αCD25-Cy7/TMZ) for precise chemotherapy and real-time immune response tracing of glioblastoma by photoacoustic-fluorescence imaging. The nanoprobe was loaded with TMZ and targeted regulatory T lymphocyte optical dye αCD25-Cy7 encapsulated by glutathione-responsive DSPE-SS-PEG2000. The results showed that the targeted efficiency of the nanoprobe to regulatory T lymphocytes is up to 92.3%. The activation of PEG/αCD25-Cy7/TMZ by glutathione enhanced the precise delivery of TMZ to the tumor microenvironment for local chemotherapy and monitored glioblastoma's boundary by photoacoustic-fluorescence imaging. Immunotherapy with indoleamine 2,3-dioxygenase inhibitors after chemotherapy could promote immunological responses and reduce regulatory T lymphocyte infiltration, which could improve the survival rate. Photoacoustic imaging has in real-time and noninvasively depicted the dynamic process of immune response on a micrometer scale, showing that the infiltration of regulatory T lymphocytes after chemotherapy was up-regulated and would down-regulate after IDO inhibitor treatment. This all-in-one theranostic strategy is a promising method for precisely delivering TMZ and long-term dynamically tracing regulatory T lymphocytes to evaluate the immune response in situ for accurate tumor chemo-immunotherapy.

In situ fluorescence-photoacoustic measurement of the changes of brown adipose tissue in mice under hindlimb unloading.

Space travel causes rapid weight loss of astronauts, but the underlying reasons are still obscure. Brown adipose tissue (BAT) is a well-known thermogenesis tissue that is innervated by sympathetic nerves, and norepinephrine stimulation can promote the thermogenesis and angiogenesis of BAT. Herein, the structural and physiological changes of BAT as well as serological indicators were investigated in mice under hindlimb unloading (HU) to simulate a weightless environment in space. The results showed that long-term HU could induced the thermogenic activation of BAT by upregulating the mitochondrial uncoupling protein. Further, peptide-conjugated indocyanine green was developed to target the vascular endothelial cells of BAT. Noninvasive fluorescence-photoacoustic imaging presented the neovascularization of BAT on the micron scale in the HU group, accompanying by the increase of vessel density. Downward trend of serum triglyceride and glucose level of mice treated with HU proved the more heat production and energy consumption in BAT compared with the control group. This study suggested that HU may be an effective strategy to curb the occurrence of obesity, whereas fluorescence-photoacoustic dual-modal imaging showed capability of assessing BAT activity.NEW & NOTEWORTHY We found that the mechanism of weight loss of astronauts in space flight may be that hindlimb unloading (HU) promotes the activation of brown adipose tissue (BAT) and the increase of uncoupling protein (UCP1) expression, which accelerates the body's heat production. Meanwhile, the activation of BAT is accompanied by the proliferation of blood vessels. With the help of peptide CPATAERPC conjugated indocyanine green targeting to vascular endothelial cells, fluorescence-photoacoustic imaging has selectively tracked the vascular structure of BAT on the micron scale, which provided noninvasive imaging tools to in situ measure the changes of BAT.

In vivo quantitative photoacoustic evaluation of the liver and kidney pathology in tyrosinemia.

Hereditary tyrosinemia type Ⅰ (HT1) is a severe autosomal recessive inherited metabolic disease, which can result in severe damage of liver and kidney. Photoacoustic imaging (PAI) uses pulsed laser light to induce ultrasonic signals to facilitate the visualization of lesions that are strongly related to disease progression. In this study, the structural and functional changes of liver and kidney in HT1 was investigated by cross-scale PAI. The results showed that the hepatic lobule and renal tubule were severely damaged during HT1 progression. The hemoglobin content, vessel density, and liver function reserve were decreased. The metabolic half-life of indocyanine green declined from 59.8 s in health to 262.6 s in the advanced stage. Blood oxygen saturation was much lower than that in health. This study highlights the potential of PAI for in vivo evaluation of the liver and kidney lesions in HT1.

Hollow terbium metal-organic-framework spheres: preparation and their performance in Fe3+ detection.

Hollow metal-organic framework (MOF) micro/nanostructures have been attracting a great amount of research interest in recent years. However, the synthesis of hollow metal-organic frameworks (MOFs) is a great challenge. In this paper, by using 1,3,5-benzenetricarboxylic acid (H3BTC) as the organic ligand and 2,5-thiophenedicarboxylic acid (H2TDC) as the competitive ligand and protective agent, hollow terbium MOFs (Tb-MOFs) spheres were synthesized by a one-pot solvothermal method. By comparing the morphology of Tb-MOFs in the presence and absence of H2TDC, it is found that H2TDC plays a key role in the formation of the hollow spherical structure. Single crystal analyses and element analysis confirm that H2TDC is not involved in the coordination with Tb3+. Interestingly, Tb-MOFs can be used as the luminescent probes for Fe3+ recognition in aqueous and N,N-dimethylformamide (DMF) solutions. In aqueous solution, the quenching constant (K SV) is 5.8 × 10-4 M-1, and the limit of detection (LOD) is 2.05 µM. In DMF, the K SV and LOD are 9.5 × 10-4 M-1 and 0.80 µM, respectively. The sensing mechanism is that the excitation energy absorption of Fe3+ ions reduces the energy transfer efficiency from the ligand to Tb3+ ions.

Hydrogen sulfide sensor based on tapered fiber sandwiched between two molybdenum disulfide/citric acid composite membrane coated long-period fiber gratings.

In this work, a novel hydrogen sulfide detection scheme based on tapered fiber seeded in two long-period fiber gratings (LPGs) coated by a molybdenum disulfide/citric acid composite membrane is proposed and fabricated. The input light of a broadband source is coupled twice by passing through two LPGs with identical parameters, from which a Mach-Zehnder interferometer can be formed. The composite sensitive membrane was prepared with molybdenum disulfide and citric acid, which was coated on the surface of the two LPGs. The experimental results show that in the range of 0-70 ppm of hydrogen sulfide, with the increase of gas concentrations the interference spectra appear to blueshift. In addition, a high sensitivity of 16.65 pm/ppm, an excellent linear relationship (R2=0.97721), and high selectivity for hydrogen sulfide are achieved. The effect of temperature is also discussed. The sensor has the advantages of low cost and small volume, and can be used for detection applications at sites where hydrogen sulfide is produced, such as natural gas plants, areas of magmatic activity, coal mines, etc.

[Seasonal stratification and eutrophication characteristics of a deep reservoir, Longtan Reservoir in subtropical area of China].

In order to reveal the seasonal stratification and eutrophication characteristics of the subtropical large deep reservoir--Longtan Reservoir, the spatial and temporal distribution of environmental factors and eutrophic index were investigated during November (dry period) 2012, April (level period) and July (wet period) 2013. The results suggested that: (1) The stratification structure of Longtan Reservoir was meromictic lake, it had a single thermocline structure in the dry season, the surface layer to the 60 m was a mixomolimnion, 60-80 m was a thermocline, deeper more than 80 m was a monimolimnion. It had a double thermocline structure in flow period and wet period, the surface to 10 m was a mixed layer, 10-20 m was a thermocline, 20-40 m was a mixed layer, 40-60 m was a thermocline, deeper more than 60 m was a mixed layer. (2) The thermal stratification dominated the structure of other environmental factors, the stratification structure limited the water convection, especially the monimolimnion reduced the harm of the endogenous pollution. (3) The trophic level index (TLI) was 23.4-32.8 in the dry period, 27.1-38.6 in the flow period and 26.0-45.1 in the wet period, which were all Mesotropher. The trophic state index of total nitrogen was 60.3-72.5, which was eutropher to hyper eutropher, N: P was 107:1, which was phosphorus limited.