Advances in macrophage-targeting nanoparticles for the diagnosis and treatment of inflammatory bowel disease / 浙江大学学报·医学版

The pathogenesis of inflammatory bowel disease (IBD) is not fully elucidated. However, it has been considered that inflammatory macrophages may be involved in the imbalance of the intestinal mucosal immunity to regulate several signaling pathways, leading to IBD progression. The ratio of M1 to M2 subtypes of activated macrophages tends to increase in the inflamed intestinal section. There are challenges in the diagnosis and treatment of IBD, such as unsatisfactory specificity of imaging findings, low drug accumulation in the intestinal lesions, unstable therapeutic efficacy, and drug-related systemic toxicity. Recently developed nanoparticles may provide a new approach for the diagnosis and treatment of IBD. Nanoparticles targeted to macrophages can be used as contrast agents to improve the imaging quality or used as a drug delivery vector to increase the therapeutic efficiency of IBD. This article reviews the research progress on macrophage-targeting nanoparticles for the diagnosis and treatment of IBD to provide a reference for further research and clinical application.

An observational study of abnormal findings in fetus during 11-13+6 weeks and targeted imaging for fetal anomalies ultrasonography

Background: Congenital anomalies are responsible for a of 14.2% of perinatal mortality in India. This study focuses on incidence of structural fetal abnormalities detected during 1st and 2nd trimester sonography. Aim of this study was to evaluate the need for targeted fetal scans.Methods: This study is an observational study conducted at Gujarat fetal medicine Centre, Ahmedabad, Gujarat, super specialty antenatal radiology centre where exclusively antenatal USGs and prenatal procedures are performed. All pregnant female coming for 1st and 2nd trimester USG were included. All fetal abnormalities in form of soft markers and structural abnormality were included.Results: Out of 2122 total ANC scans, 183 cases (8.6%) had structural abnormality and 235 cases (11%) had significant soft markers. 1185 cases (55.84%) came in late 2nd trimester for TIFFA scan and 468 (22%) were seen in 1st trimester scan. The incidence of fetal anomaly in this study was higher than general population as it is an exclusively fetal medicine centre and majority of patients were diagnosed with anomaly in late 2nd trimester.Conclusions: There is immense need for early diagnosis and timely intervention before 20 weeks in case of prenatal detection of fetal abnormality.

Near-Infrared Contrast Agents for Bone-Targeted Imaging

BACKGROUND: For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. METHODS: The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. RESULTS: A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. CONCLUSION: By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.

Click-Functionalized Fluorescent Nanoprobes with Folate Receptor-Targeting Ability for Cancer Cell Imaging / 分析化学

Folate receptor ( FR )-targeted fluorescent nanoprobes ( RSiNPs-Folate ) were constructed by modifying Rubpy-doped silica nanoparticles ( RSiNPs) with folic acid ( FA) based on click chemistry coupling method, which was successfully used for cancer cell imaging. Firstly, RSiNPs were prepared by St?ber method and modified with azide groups through the hydrolysis of silane coupling agents ( Az-PTES ) , then propargyl folate were conjugated onto the nanoparticle surfaces via click reaction. It was demonstrated that the FA-functionalized nanoprobes were successfully prepared by monitoring the characteristic peak of the azide group at 2105 cm-1 before and after coupling. In the condition of physiological pH, the nanoprobes exhibited strong red emission at 601 nm when excited at the 458 nm excitation wavelength. The cell imaging results showed that RSiNPs-Folate could effectively target FR-positive HeLa cells, while no obvious fluorescence was observed for FR-negative A549 cells. The receptor-mediated imaging mechanism was confirmed by free FA competition experiments. More importantly, HeLa cells could be selectively recognized and imaged in the mixing cell system. Compared with the carbodiimide conjugation protocols, the click-functionalized nanoprobes had many advantages such as simple synthesis procedures, mild reaction conditions and high yields, which could be potentially used for fluorescent labeling and imaging of different cancer cells.

Specific MR imaging of hepatocellular carcinoma with VEGF-C targeted USPIO probe in a rat model / 实用放射学杂志

Objective To investigate the potential value of VEGF-C targeted ultrasmall superparamagnetic particles of iron oxide (USPIO)molecular probe in specific detection of hepatocellular carcinoma (HCC)in a rat model using MRI.Methods The targeted probe was synthesized by conjugating VEGF-C antibody with amino modified USPIO.Cell counting kit-8 assay was conducted to as-certain the probe’s effect on the growth of HepG2 cells.Rat models with HCC were divided into two groups (targeted group with VEGF-C-USPlO and a contrast with USPIO)with 3 rats for each group at random.Pre-and post-contrast enhanced MR imaging with different time points of 0.5,1 and 1.5h was performed with an injection into caudal vein.The signal intensities of the tumor on T2 WI and T2 * WI were measured,and the differences of the signal intensities between pre-and post-enhancements or between both groups were analyzed.The iron particles within the tumors in two groups were confirmed by Prussian blue iron staining.The ex-pression of VEGF-C in HCC was proved by immunohistochemistry.Results The signal intensities of HCC on T2 WI and T2 * WI af-ter VEGF-C-USPI0 injection were decreased obviously with a minimum value at 1 h ,indicating a significant difference (P 0.05).Statistical differences in signal inten-sity on T2 * WI after enhancement between both groups were also showed (P <0.05).Prussian blue staining results showed more iron particles within the tumor tissues in VEGF-C-USPI0 group,whereas less ones in USPIO group.Immunohistochemical results showed that VEGF-C was over expressed in cytoplasm and membrane.Conclusion VEGF-C-USPI0 molecular probes can initiatively target to the liver cancer in rat models with expressed VEGF-C,which may help to achieve the specific MR imaging of HCC,indica-ting a potential of the metastasis.

Synthesis of the PLA-PEG-PLL gadolinium loaded nanoprobe targeted to vascular endothelial growth factor used for the molecular imaging of micro-hepatic carcinoma / 中华肝胆外科杂志

Objective This study aims to synthesize a novel gadolinium loaded nanoprobe targeted to vascular endothelial growth factor (VEGF) and assess its clinical value for imaging micro hepatic carcinoma.Methods A carrier was made by the biocompatible polymer material polylactic acid-polyethylene glycol-poly-L-lysinenanoparticles (PLA-PEG-PLLs).The targeted nanoprobe was obtained with anti-VEGF antibody and gadolinium (Gd) bonding to the surface of the carrier.MRI in vitro determined the T1 relaxivity of the nanoprobe.A live cancer model enhanced MR scan was performed by injecting targeted nanoprobes into the tail vein of grafted H22 tumor mice.The enhanced characteristics of the subcutaneous tumors and micro-heatic carcinoma were then reviewed.Results The particle size of the VEGF-targeted PLA-PEG-PLL gadolinium loaded nanoprobe was 85.8±7.2 nm with a zeta potential of 21.63±2.4 mV.The R1 relaxivity of the targeted nanoprobe was 18.394 mmol/s at 3.0 T when its gadolinium concentration was 8.0 μmol/ml.The enhanced MR scan using targeted probes showed that the big and micro-subcutaneous cancer exhibited a specifically delayed enhancement with an enhanced peak value at 2 or 3 hours,rather than the enhancement of the tumor using the nontargeted nanoparticles.Conclusion In conclusion,the VEGF targeted PLA-PEG-PLL gadolinium loaded nanoprobe was synthesized successfully,showed a high relaxivity,achieved targeted imaging of the micro-hepatic carcinoma,and exhibits a promising potential in the detection of this liver cancer.