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NUCLEAR MEDICINE AND BIOLOGY · 2024 · IF 3.6

Serotonin transporter imaging agent as a probe for β-cells of pancreas

Yuli Sun,Guangwen Li,Haiyan Hong,Lin Zhu,Hank F. Kung,Yan Zhang,Jinxia Zhu

Objective Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo , which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [ 125 I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). Methods In vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. Results In vitro cell studies showed that the concentration of [ 125 I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [ 125 I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. Conclusions The SERT imaging agent, [ 125 I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.

研究领域: 医学影像学 · 内分泌学 · 糖尿病研究
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Science Advances · 2023 ·Vol. 9 ·期 19 · IF 13.6

Swarming self-adhesive microgels enabled aneurysm on-demand embolization in physiological blood flow

Dongdong Jin,Qinglong Wang,Kai Fung Chan,Neng Xia,Haojin Yang,Qianqian Wang,Simon Chun Ho Yu,Li Zhang

The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.

研究领域: 医学工程 · 生物材料学 · 微创治疗 · 机器人技术
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ACS Nano · 2018 · IF 13.709

Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine

Shasha He,Chan Li,Qingfei Zhang,Jianxun Ding,Xing-Jie Liang,Xuesi Chen,Haihua Xiao,Xiaoyuan Chen,Dongfang Zhou,Yubin Huang

Drug, targeting ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose targeting ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine.

研究领域: 纳米技术 · 药学 · 癌症研究 · 材料科学 · 生物医学工程
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ADVANCED FUNCTIONAL MATERIALS · 2021 ·Vol. 31 ·期 24 ·2100936 · IF 18.808

Biocompatible Nanomotors as Active Diagnostic Imaging Agents for Enhanced Magnetic Resonance Imaging of Tumor Tissues In Vivo

Shaohui Zheng,Yong Wang,Sihao Pan,Enhui Ma,Shang Jin,Min Jiao,Wenjun Wang,Jingjing Li,Kai Xu,Hong Wang

The limited penetration of imaging agents in solid tumor tissue and cells remains a great challenge to achieve ideal visibility in cancer diagnosis. Herein, a near infrared (NIR) light-driven Janus mesoporous silica nanomotor (JMS nanomotor) to promote magnetic resonance (MR) imaging in vivo is developed. The JMS nanomotors are prepared by depositing Au on the half-sphere surface of gadolinium-doped mesoporous silica nanoparticles. Under NIR irradiation, the nanomotors achieve efficient propulsion through thermophoresis in biological media. To prove the ability of nanomotors as active diagnostic imaging agents, both in vitro and in vivo experiments are carried out. In vitro studies confirm that NIR light can actively propel the JMS nanomotors to effectively seek, adhere to, and mechanically perforate the tumor cells to enhance the cellular uptake and MR imaging. To move a step further, in vivo investigations show that the JMS nanomotors also exhibit improved accumulation and deep penetration in the solid tumor model when exposed to NIR laser, where the MR imaging contrast is significantly enhanced in the majority of tumor tissue. Such JMS nanomotors provide new insight in precise cancer diagnosis and meanwhile MR imaging offers a new tool for real-time tracking of nanomotors in vivo.

研究领域: 生物医学工程 · 纳米技术 · 癌症诊断 · 磁共振成像
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JOURNAL OF MOLECULAR STRUCTURE · 2023 · IF 3.8

Design, synthesis and evaluation of benzo[cd]indol-2(1H)-one-donepezil hybrids as cholinesterase inhibitors and living cell imaging agents

Junjie Wang,Hui Zhou,Yang Li,Yeshu Mu,Jinghua Li,Chen Hong,Wen Luo

A novel series of benzo[ cd ]indol-2(1 H )-one-donepezil (BIO-DPZ) hybrids (5a-m, 6a-k) was designed, synthesized and evaluated as cholinesterase inhibitors and living cell imaging agents. These compounds were potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compound 6a exhibited the strongest inhibitory activity against AChE with an IC 50 value of 0.16 μM. Compound 6i had the strongest inhibition of BuChE with an IC 50 value of 5.37 μM. Kinetic and molecular modeling studies showed that 6a bound both catalytic active site and peripheral anionic site of AChE. Compounds 6a and 6i both showed lower SH-SY5Y, HepG2 and HL-7702 cytotoxicity than the mitoxantrone. Promisingly, the most active compound, 6a, was successfully used in living SH-SY5Y cell imaging and had predictable lipophilicity and blood-brain-barrier permeation properties. These hybrids should undergo further systematic study in the treatment of Alzheimer's disease.

研究领域: 药理学 · 神经科学 · 药物化学
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BIOCONJUGATE CHEMISTRY · 2016 · IF 4.5

Redox-Sensitive Citronellol–Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine

Peng Xue,Dan Liu,Jing Wang,Na Zhang,Jiahua Zhou,Lin Li,Weiling Guo,Mengchi Sun,Xiangfei Han,Yongjun Wang

Citronellol-cabazitaxel (CIT-ss-CTX) conjugate self-assembled nanoparticles (CSNPs) were designed and prepared by conjugating cabazitaxel with citronellol via the disulfide bond that is redox-sensitive to the high concentration of glutathione within tumor cells. Notably, the CSNPs maintained in the cell cytotoxicity. Moreover, the AUC0-t of CSNPs was 6.5-fold higher than that of cabazitaxel solutions and the t1/2 was prolonged 2.3 times. Furthermore, we found that CSNPs could be employed as an efficient carrier for other hydrophobic drugs or imaging agents. Thus, the in vivo targeting study was implemented via using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-loaded CSNPs as imaging agent, which showed CSNPs could effectively accumulate at the tumor site. Curcumin, a hydrophobic anticancer drug, was successfully loaded in CSNPs which exhibits good stability and synergistic antitumor effects. The citronellol–cabazitaxel conjugate therefore has a promising perspective as a multifunctional nanomedicine for combination therapy and theranostics attributed to its long-circulation property, redox-sensitive mechanism, and high drug coloading capability.

研究领域: 药学 · 纳米技术 · 肿瘤学 · 药物递送系统 · 诊疗一体化
✓ 已验证 产品关联 DOI PubMed 高影响因子
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