DRUG DELIVERY
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2021
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IF 6.419
Jiali Li,Xue Jiang,Lihuan Shang,Zhen Li,Conglian Yang,Yan Luo,Daoyu Hu,Yaqi Shen,Zhiping Zhang
This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn2+ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM−1·s−1. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.
研究领域:
医学影像学
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纳米医学
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生物材料
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DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 20
·6929
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IF 4.927
Lei Yang,Mohammad Javad Afshari,Jianxian Ge,Dandan Kou,Lei Chen,Dandan Zhou,Cang Li,Shuwang Wu,Leshuai Zhang,Jianfeng Zeng,Jian Zhong,Roland H. Stauber,Mingyuan Gao
Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitiveT1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia viaT1-weighted MRI. These promising results may unlock the potential of Fe3O4nanoparticles asT1-weighted contrast agents for the development of clinical hypoxia probes.Keywords:tumor hypoxia;ultrasmall iron oxide nanoparticles;magnetic resonance imaging;metronidazole
研究领域:
医学影像
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纳米技术
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
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IF 4.511
Ting Tang,Xiaojie Ma,Yifeng Bian,Zhiyao Yuan,Duohong Zou,Ning Chen
Magnetic resonance contrast agent employs the use of gadolinium chelates, which has many limitations for clinical use including a low contrast effect, a short diagnostic window, and a brief blood circulation time. On this basis, we designed a gadolinium-labeled dendrimer nanocluster (GdDN) loaded graphene oxide nanosheet (GO-GdDN) to boost T1 contrast ability for imaging in vivo and improve blood circulation time. GO-GdDN presented an ultrahigh r1 relaxivity up to 19.07 mM–1 s–1 in a 9.4 T MR scanner, and a bright contrast image in vitro experiment. In addition, GO-GdDN could be internalized by HepG2 cells and presented strong cell contrast enhancement and reduction of the T1 value in HepG2 cells. In vivo, the retention time of GO-GdDN was significantly improved, so that the accumulation of GO-GdDN in liver was enhanced. Moreover, compared to Gd-DTPA, systemic delivery of GO-GdDN dramatically enhanced the signal-to-noise ratio of liver images, which was helpful for accurate imaging of liver and detection of liver lesions in vivo. Thus, this study demonstrates the utility of a powerful diagnosis tool for liver tumor or lesions.
研究领域:
医学影像学
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纳米医学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
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2024
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IF 8.1
Yufang Gong,Kai Guo,Siyu Cai,Ke Ren,Liya Tian,Yingqi Wang,Mengyao Mu,Qingwei Meng,Jie Liu,Xiao Sun
The impact of nanoparticle size on the effectiveness of magnetic resonance imaging (MRI) using sulfurized manganese nanoparticles (MnS@PAA) stabilized with polyacrylic acid (PAA) as a binder was thoroughly investigated. MnS@PAA nanoparticles of varying sizes were synthesized by altering the ratio of ethylene glycol (EG) to diethylene glycol (DEG) during the synthesis process. These nanoparticles exhibited a uniform size distribution and demonstrated high T1 relaxation rates, along with a notable pH-responsive behavior. As the nanoparticle size increased, the T1 relaxation rate decreased, indicating that size plays a crucial role in their MRI performance. Additionally, research has revealed that the efficiency of tumor uptake by these nanoparticles is size dependent. Specifically, MnS@PAA nanoparticles with a core size of 100 nm (MS100) exhibited greater tumor accumulation and provided enhanced MRI contrast. Once within the acidic environment of a tumor, MS100 decomposes into Mn2+ and H2S. Mn2+ ions promote the generation of hydroxyl radicals, which leads to lipid peroxidation and induces ferroptosis. Concurrently, the release of H2S inhibits catalase activity, resulting in elevated levels of hydrogen peroxide (H2O2), achieving a synergistic effect between chemodynamic therapy (CDT) and gas therapy. This study explores the influence of nanoparticle size on its potential applications as an MRI contrast agent and as a therapeutic agent in cancer treatment.
研究领域:
医学影像学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Maojuan Liu,Yunhe Li,Yang Song,Erqun Song
Peritoneal dialysis-associated peritonitis (PDAP), primarily caused by bacterial infections, is a severe complication and a major contributor to mortality in peritoneal dialysis patients. Early detection of bacterial infections and prompt therapeutic interventions are critical for effective PDAP management. Herein, we report the development of a novel apoptotic body (AB)-hitchhiked manganese-based T1-weighted magnetic resonance imaging (MRI) probe (PMA) for noninvasive and in situ bacterial detection in the abdominal cavity, offering a potential early warning system for PDAP. When administered to PDAP model mice, the PMA probes selectively accumulated in bacteria-infected regions via AB-mediated macrophage targeting. Subsequently, the PMA probes disintegrated in the acidic microenvironment of bacterial infection, which resulted in the MRI signal ON, therefore imaging the bacterial infection in vivo accurately. Remarkably, due to the protein-assisted T1-weighted signal amplification, the PMA probe-based MRI strategy detected bacterial loads in the abdominal cavity approximately 10 times lower than those identified by biochemical analysis for PDAP diagnosis. This approach achieves sensitive bacterial detection, holding great potential for the early diagnosis of PDAP in clinical practice in the future.
研究领域:
微生物学
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影像医学
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生物材料
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转化医学
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肾脏病学
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分子诊断
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
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2025
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IF 4.2
Lichang Lei,Hongjiao Zi,ShaoLei Kang,Hui Duan,Zhenghua Zhang,Chao Gao,Ruoyun Xu,Dan Han
Introduction: Magnetic Resonance Imaging (MRI)-guided photothermal therapy (PTT) holds significant promise for the treatment of solid tumors, however, its diagnostic and therapeutic efficacy in malignant pleural mesothelioma (MPM) remains underexplored. To address the limitations of traditional gadolinium (Gd)-based MRI contrast agents, such as intolerance in patients with renal insufficiency and T1 signal attenuation at high field strengths, as well as oxidative stress damage caused by manganese ion leakage from manganese-based materials, this study aims to develop highly chelated and stable manganese polydopamine (Mn-PDA) multifunctional nanoprobes for MRI monitoring and PTT treatment of MPM.Methods: Mn2+ and dopamine were chelated into Mn-PDA NP nanospheres in an ethanol-water system. The physicochemical properties were characterized using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential, Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Photoelectron Spectroscopy (XPS), and Electron Paramagnetic Resonance (EPR). The photothermal performance under 808 nm laser irradiation was also evaluated. The MRI imaging performance (longitudinal/transverse relaxation rates, r1/r2) and manganese ion deposition quantification of Mn-PDA NPs were evaluated in vitro and in vivo at 3.0 T MR scanner. Additionally, the PTT efficacy of Mn-PDA NPs was evaluated in MSTO-211H cells and xenograft tumor models. Biocompatibility was assessed through H&E staining of major organs and blood biochemical analyses.Results: Mn-PDA NPs exhibited a spherical morphology with uniform size (∼200 nm), along with high photothermal conversion efficiency, favorable T1-weighted MRI contrast enhancement and low cytotoxicity. At 8 hours post-injection in vivo, Mn-PDA NPs resulted in a 42.9% enhancement in T1-weighted MRI signals within MPM tumors, accompanied by specific tumor accumulation. Under 808 nm laser irradiation, Mn-PDA NPs inhibited MPM tumor growth, as evidenced by reduced tumor volume, expanded areas of tumor necrosis (H&E staining), and downregulated Ki-67 expression. Moreover, stable body weight, normal histological features of major organs, and unaltered blood biochemical parameters were observed in the animals.Discussion: These findings indicate that Mn-PDA NPs are effective dual-functional agents, serving as both MRI contrast agents and photothermal therapeutics. They exhibit good tumor targeting ability, excellent imaging performance, potent therapeutic efficacy, and high biosafety, thereby offering a promising therapeutic strategy for MPM management.
研究领域:
肿瘤学
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纳米医学
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影像诊断学
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转化医学
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生物材料学
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分子影像学
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光热治疗
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2020
·Vol. 8
·期 7
·1507-1515
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IF 5.344
Kai Xu,Zhenghuan Zhao,Junfeng Zhang,Wei Xue,Haipeng Tong,Heng Liu,Weiguo Zhang
Mn(IV)-Based nanoparticles (NPs) are effective in improving tumor oxygenation (hypoxia) and reducing endogenous hydrogen peroxide and acidity in the tumor region. However, the optimized reduction conditions of conventional Mn(IV)-based NPs are generally reported at pH ≤ 6.5, while the usual pH range of the tumor microenvironment (TME) is 6.5–7.0. The dissatisfactory imaging performance in the weakly acidic environment may limit their further application in tumor diagnosis. In this study, Mn(III) was introduced in a nanoplatform, because it is reduced into Mn(II) in weakly acidic environments. Arg-Gly-Asp (RGD) peptide-decorated bovine serum albumin (BSA) was employed as the stabilizer and scaffold to fabricate Mn(III)- and Mn(IV)-integrated nanocomposites (RGD-BMnNPs) with suitable size, good stability, and excellent biocompatibility. The as-prepared NPs showed clear contrast enhancement at pH 6.5–6.9 in vitro as well as sensitive and rapid T1-weighted imaging performance within the tumor region in a glioblastoma (U87MG) orthotopic model, owing to the intrinsic disproportionation reaction of Mn(III) in the weakly acidic environment. In addition, these NPs could be used for efficient siRNA delivery. They showed superior advantages in this process, including increased tumour uptake, improved tumor accumulation and enhanced therapeutic effects with the modulation of the TME. These novel albumin-stabilized manganese-based NPs combined with efficient drug delivery capacity hold great potential to serve as intelligent theranostic agents for further clinical translation.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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神经科学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Gongxin Yang,Jikai Xia,Xiaoqing Dai,Hongbo Zhao,Weiqing Gao,Weilong Ding,Xiaofeng Tao,Ling Zhu
Introduction Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.Methods Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).Results The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.Conclusion Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.
研究领域:
医学影像
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纳米技术
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癌症诊断
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2023
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IF 5.7
Ruru Zhang,Kuan Lu,Li Xiao,Xuelan Hu,Wu Cai,Linjiang Liu,Yan Liu,Weihua Li,Hui Zhou,Zhiyuan Qian,Sixia Wang,Can Chen,Jianfeng Zeng,Mingyuan Gao
Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.
研究领域:
医学影像学
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纳米技术
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心血管疾病
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分子成像
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Na Tang,Yi Zhu,Ziwei Lu,Jiali Deng,Jiajing Guo,Xinyi Ding,Jingyi Wang,Rong Cao,An Chen,Zhongyi Huang,Hongwei Lu,Zhongling Wang
MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.
研究领域:
肿瘤学
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生物医学工程
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纳米技术
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医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）