Construction of a Tumor-Targeting Nanobubble with Multiple Scattering Interfaces and its Enhancement of Ultrasound Imaging.

Introduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection. Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo. Results: The results show that IR783-SiO2NPs@NB had a "donut-type" composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability. Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.

Development of a Gold Nanoparticle-Linked Immunosorbent Assay of Staphylococcal Enterotoxin B Detection with Extremely High Sensitivity by Determination of Gold Atom Content Using Graphite Furnace Atomic Absorption Spectrometry.

Highly sensitive staphylococcal enterotoxin B (SEB) assay is of great importance for the prevention of toxic diseases caused by SEB. In this study, we present a gold nanoparticle (AuNP)-linked immunosorbent assay (ALISA) for detecting SEB in a sandwich format using a pair of SEB specific monoclonal antibodies (mAbs) performed in microplates. First, the detection mAb was labeled with AuNPs of different particle sizes (15, 40 and 60 nm). Then the sandwich immunosorbent assay for SEB detection was performed routinely in a microplate except for using AuNPs-labeled detection mAb. Next, the AuNPs adsorbed on the microplate were dissolved with aqua regia and the content of gold atoms was determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, a standard curve was drawn of the gold atomic content against the corresponding SEB concentration. The detection time of ALISA was about 2.5 h. AuNPs at 60 nm showed the highest sensitivity with an actual measured limit of detection (LOD) of 0.125 pg/mL and a dynamic range of 0.125-32 pg/mL. AuNPs at 40 nm had an actual measured LOD of 0.5 pg/mL and a dynamic range of 0.5 to 128 pg/mL. AuNPs at 15 nm had an actual measured LOD of 5 pg/mL, with a dynamic range of 5-1280 pg/mL. With detection mAb labeled with AuNPs at 60 nm, ALISA's intra- and interassay coefficient variations (CV) at three concentrations (2, 8, and 20 pg/mL) were all lower than 12% and the average recovery level was ranged from 92.7% to 95.0%, indicating a high precision and accuracy of the ALISA method. Moreover, the ALISA method could be successfully applied to the detection of various food, environmental, and biological samples. Therefore, the successful establishment of the ALISA method for SEB detection might provide a powerful tool for food hygiene supervision, environmental management, and anti-terrorism procedures and this method might achieve detection and high-throughput analysis automatically in the near future, even though GFAAS testing remains costly at present.

Uptake Quantification of Antigen Carried by Nanoparticles and Its Impact on Carrier Adjuvanticity Evaluation.

Nanoparticles have been identified in numerous studies as effective antigen delivery systems that enhance immune responses. However, it remains unclear whether this enhancement is a result of increased antigen uptake when carried by nanoparticles or the adjuvanticity of the nanoparticle carriers. Consequently, it is important to quantify antigen uptake by dendritic cells in a manner that is free from artifacts in order to analyze the immune response when antigens are carried by nanoparticles. In this study, we demonstrated several scenarios (antigens on nanoparticles or inside cells) that are likely to contribute to the generation of artifacts in conventional fluorescence-based quantification. Furthermore, we developed the necessary assay for accurate uptake quantification. PLGA NPs were selected as the model carrier system to deliver EsxB protein (a Staphylococcus aureus antigen) in order to testify to the feasibility of the established method. The results showed that for the same antigen uptake amount, the antigen delivered by PLGA nanoparticles could elicit 3.6 times IL-2 secretion (representative of cellular immune response activation) and 1.5 times IL-12 secretion (representative of DC maturation level) compared with pure antigen feeding. The findings above give direct evidence of the extra adjuvanticity of PLGA nanoparticles, except for their delivery functions. The developed methodology allows for the evaluation of immune cell responses on an antigen uptake basis, thus providing a better understanding of the origin of the adjuvanticity of nanoparticle carriers. Ultimately, this research provides general guidelines for the formulation of nano-vaccines.

The effect of oral nutritional supplements on the nutritional status of community elderly people with malnutrition or risk of malnutrition.

BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplements (ONS) on community elderly people with malnutrition or risk of malnutrition. METHODS AND STUDY DESIGN: A single arm intervention trial for 3 months was conducted. Whole nutrient powder was given to all the participants. Dietary intakes were measured by 3-day diet record. Nutritional status was evaluated using body weight, body mass index (BMI), calf circumference (CC), and Mini Nutritional Assessment Short-Form (MNA-SF) scores. Muscle mass was measured by bioimpedance analysis (BIA). All these parameters as well as muscle strength, physical function, and quality of life were measured at both the baseline and the end. RESULTS: Compared with the baseline, ONS increased protein intake (58.32±16.67 vs 41.90±18.49 g/d, p<0.001), body weight (57.03±8.31 vs 56.68±8.23 kg, p<0.05), BMI (22.16±2.13 vs 22.02±2.08 kg/m2, p<0.05), CC (34.21±2.53 vs 33.80±2.53 cm, p<0.001), MNA-SF scores (12.61±1.43 vs 10.48±0.99, p<0.05), hand grip strength (24.54±8.05 vs 23.27±7.74 kg, p<0.001), and 6-m gait speed (1.11±0.33 vs 0.96±0.28 m/s, p<0.001). Moreover, SF-36 scores of the overall subjects have been improved in all dimensions (p<0.05). CONCLUSIONS: The study demonstrated that ONS can effectively increase protein intake and improve nutritional status, muscle strength, physical function and quality of life of the elderly with malnutrition or malnutrition risk in communities.