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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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2026
·
IF 5.6
Wang Peng,Xia Jikai,Wang Hanjing,Liu Qingxin,Gao Wenjuan,Zhang Guilong
The highly efficient, tumor-specific targeting capability of contrast agents enables accurate cancer diagnosis via magnetic resonance imaging (MRI). In this study, a homologous targeting T 1 MRI probe with pH-responsive properties was developed for precise diagnosis of triple-negative breast cancer. MnCO 3 nanoclusters, as a T 1 MRI contrast agent, respond to the acidic tumor microenvironment by releasing paramagnetic Mn 2+ ions. Subsequently, deactivated 4T1 cells, treated by freezing to preserve their cell membrane, were employed as biomimetic carriers for MnCO 3 (d4T1@Mn), serving as the homologous targeting T 1 MRI probe. Compared to traditional cancer cell membrane-camouflaged nanoplatforms (Cm@Mn) and Mn-DPDP, this T 1 MRI probe, owing to its intact cell membrane structure and superior homologous targeting capability, enhances contrast agent accumulation at the tumor site, intensifies T 1 -weighted MR signals in the tumor region, significantly improves the signal-to-noise ratio and tumor-to-muscle ratio, and provides an extended optimal imaging window, thereby enabling precise diagnosis of triple-negative breast cancer. In vivo studies further demonstrated that systemic administration of the MRI probe did not induce blood or tissue damage, confirming its excellent biocompatibility. In conclusion, this approach successfully introduces an effective tumor-specific T 1 MRI probe, improving tumor diagnosis accuracy in MRI.
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高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Manman Xie,Ziyang Wang,Qian Lu,Shuming Nie,Christopher J. Butch,Yiqing Wang,Bo Dai
Herein, we present a new magnetic iron oxide nanoparticle (MION) with a succinylated heparin monolayer coating, which exhibits the highest T1 relaxivity at 7 T and the lowest r2/r1 reported for any MION at these high-field conditions. While the recent proliferation of 7 T MRI instruments in hospitals worldwide has enabled widespread access to higher quality, more finely detailed, diagnostic imaging, clinically available contrast agents have not kept pace due to the general phenomenon of reduced efficacy of T1 relaxation as magnetic field strength is increased. Development of new MION agents is one strategy to address this need, and to this end, we demonstrate the in vitro magnetic properties of the MIONs reported here to extend to in vivo applications, providing greatly increased contrast in tumor imaging in a murine xenograft subject at 7 T. While MION-based contrast agents can have side effects in clinical application, these are generally thought to be less than those of gadolinium-based agents and here are further reduced by the small size allowing direct glomerular filtration from the blood followed by renal-excretion. Finally, we show the succinylated heparin monolayer coating to provide class leading magnetic properties over a homologous series of particles with core size ranging from 2 to 18 nm and show the properties to be strongly related to the surface area. We suggest the increased porosity and hydrophilicity of the coating to increase water accessibility to the surface resulting in the increased magnetic properties.
研究领域:
医学影像学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
GIANT
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2022
·
IF 0
Yifan Jia,Weiwen Yuan,Mengmeng Xu,Congyi Yang,Lei Chen,Shuo Wang,Paul D. Topham,Guoxuan Luo,Mo Wang,Yong Zhang,Guihua Jiang,Qianqian Yu,LinGe Wang
Magnetic resonance imaging (MRI)-active polymers exhibit unique advantages for in vivo diagnosis. Here, in order to endow electrospun fibers with long-term T 1 positive MRI visibility, MRI contrast agent (CA), Gd(OH) 3 , is introduced in a new, extremely convenient method. Crucially, GdCl 3 is reacted with NaOH in situ during electrospinning, with flexibility to deliver both well-dispersed and aggregated Gd(OH) 3 clusters within a poly(ethylene terephthalate) (PET) matrix. T 1 and T 2 relaxivities of Gd(OH) 3 in PET nanofibers are studied. Well-dispersed Gd(OH) 3 (sub-nanometer in size) exhibits 34 times higher T 1 relaxivity than aggregated nanoparticles when embedded within the fibers. The morphology, structure, magnetic properties, tensile properties, imaging performance and biosafety of the PET/Gd(OH) 3 composite fibers are evaluated to identify the optimum conditions to produce new materials with balanced properties, excellent in vivo positive contrast and approximately 139 days imaging lifetime. Comparing this sample with a commercial CA, only 0.32 wt.% Gd loading is needed to attain similar MRI signal intensity. In summary, PET/Gd(OH) 3 long-term MRI-active fibers show great potential for future biomedical applications and the study also provides a promising new general strategy to enhance the MRI T 1 positive contrast of electrospun fibers of a whole host of other systems.
研究领域:
材料科学
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医学影像学
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生物医学工程
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DOI
Nano Research
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2017
·Vol. 11
·期 2
·929-939
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IF 7.354
He Zhimei,Zhang Penghui,Xiao Yan,Li Jingjing,Yang Fang,Liu Yang,Zhang Jian-Rong,Zhu Jun-Jie
During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T 1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and “turned on” T 1 signals in vitro , showing great promise for diagnosis and treatment.
研究领域:
癌症治疗
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纳米技术
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药物递送系统
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磁共振成像
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生物医学工程
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DOI
高影响因子
Journal of Materials Chemistry B
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2023
·Vol. 11
·期 29
·6889-6895
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IF 7
Qian Song,Bin Chi,Haiqing Gao,Junke Wang,Miaomiao Wu,Yi Xu,Yingxi Wang,Zushun Xu,Ling Li,Jing Wang,Run Zhang
Nanozyme-based tumour catalytic therapy has attracted widespread attention in recent years, but the therapeutic efficacy is limited due to the trapping of hydroxyl radicals (˙OH) by endogenous glutathione (GSH) in the tumour microenvironment (TME). Zr/Ce-MOFs/DOX/MnO2 is constructed in this work to serve as a new kind of nanozyme for combination chemotherapy and catalytic treatment. Zr/Ce-MOFs can produce ˙OH in a mimic TME, and the MnO2 on the surface could deplete the GSH, further promoting the ˙OH generation. The pH/GSH dual stimulation accelerates the release of anticancer drug doxorubicin (DOX) in tumour tissue for enhanced tumour chemotherapy. Moreover, Mn2+ produced by the reaction of Zr/Ce-MOFs/DOX/MnO2 and GSH can be used as the contrast agent for T1-MRI. The potential antitumour effect of Zr/Ce-MOFs/DOX/MnO2 is demonstrated by in vitro and in vivo cancer treatment tests. This work thus provides a new nanozyme-based platform for enhanced combination chemotherapy and catalytic treatment for tumours.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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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
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Meirong Hou,Kai Zhu,Honglei Hu,Shuting Zheng,Zede Wu,Yunyan Ren,Bin Wu,Li Qi,Dong Wu,Yikai Xu,Chenggong Yan,Bingxia Zhao
Though amounts of attempts about nanomedicine for chemo-radiotherapy have been made, more efficient strategies for chemo-radio therapy enhancement still need to be studied and perfected. Herein, a ‘yolk-shell’-like nanostructure (Bi 2 S 3 @mBi x Mn y O z nanosystem) was facilely constructed by directly using radiosensitizer Bi 2 S 3 nanorods (NRs) as a partial sacrificial template. Then, the chemotherapeutic drug doxorubicin (DOX) loaded PEGylated Bi 2 S 3 @mBi x Mn y O z nanosystem (PBmB-DOX) was constructed, which could realize tumor microenvironment (TME)-responsive drug release for chemotherapy sensitivity enhancement. And the Bi 2 S 3 NRs core could deposit more radiant energy to improve the radiotherapy sensitivity. Meanwhile, the compounds shell could catalyze H 2 O 2 to generate O 2 , so as to alleviate tumor hypoxia for further chemo-radio therapy sensitization enhancement. More importantly, ferroptosis was participated in the process of PBmB-induced therapy via glutathione (GSH)-depletion mediated GPX4 inactivation, together with Mn ions induced chemodynamic therapy (Fenton-like reaction), which made additional contributions to increase the therapeutic efficacy. Last but not least, the GSH-stimulated degradation of compounds shell could contribute to self-enhanced T 1 -MR imaging activation, which allowed on-demand tumor diagnosis. In this work, the synthetic strategy that directly using Bi 2 S 3 NRs as a partial sacrificial template to rapidly synthesize the ‘yolk-shell’-like nanostructure for nanomedical application has rarely been reported before. And the in vitro and in vivo results suggest that our ‘yolk-shell’-like PBmB-DOX nanosystem holds great promise to regulate TME for tumor-specific diagnosis and synergistic therapy.
研究领域:
纳米医学
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癌症治疗
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材料科学
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医学成像
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化学工程
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PubMed
高影响因子
ACS Nano
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2023
·
IF 17.1
Weitao Yang,Cuijun Deng,Xiudong Shi,Yan Xu,Chenyu Dai,Hui Wang,Kexin Bian,Tianming Cui,Bingbo Zhang
Enhanced imaging techniques using contrast agents enable high-resolution structural imaging to reveal space-occupying lesions but rarely provide detailed molecular information. To this end, we report a structural and molecular fusion magnetic resonance imaging (MRI) nanoprobe for differential diagnosis between benign and malignant tumors. This fusion nanoprobe, termed FFT NPs, follows a working mechanism involving a T1-/T2-weighted magnetic resonance tuning effect (MRET) between a magnetic Fe3O4 core and a paramagnetic Fe-tannic acid (Fe-TA) shell. The FFT NPs with an “always-on” inert T2 signal provide structural MRI (sMRI) contrast of tumors while affording an activated T1 signal in the presence of ATP, which is overproduced during the rapid growth of malignant tumors to enable molecular MRI (mMRI) of tumor lesions. We propose the use of the ratiometric mMRI:sMRI intensity to assist in the differential diagnosis of malignant 4T1 tumors from benign L929 fibroblast tumors. Furthermore, the dissociated FFT NPs were found to be able to catalyze H2O2 conversion in 4T1 tumors to generate excess reactive oxygen species (ROS) for chemodynamic therapy. The described fusion nanoprobe strategy enables the differential diagnosis of tumors from a combined spatial and molecular perspective with one-stop MRI imaging with potential applications in precision intervention.
研究领域:
医学影像
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纳米技术
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癌症研究
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分子生物学
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诊疗学
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DOI
PubMed
高影响因子
NMR IN BIOMEDICINE
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2025
·Vol. 38
·期 9
·e70116
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IF 2.7
Fei-Xiang Hu,Deng-Deng Liu,Xiao-Wen Ma,Pu-Yeh Wu,Wei-Jun Peng,Dan Wang,Tong Tong
This study aims to design and evaluate a two-dimensional Ti 3 C 2 -MXene contrast agent, codoped with iron and manganese, with the aim of achieving T 1 /T 2 dual-mode magnetic resonance imaging contrast, and to investigate its effect on Chemical Exchange Saturation Transfer (CEST) contrast agents. Single-layer Ti 3 C 2 was synthesized via the HCL/LiF etching technique, with the flake size subsequently tailored and the hydroxylated surface modified through a hydrothermal process. Fe 3 O 4 nanoparticles and MnO 2 nanosheets were integrated onto the two-dimensional Ti 3 C 2 -MXene surface using an in situ doping approach, and the final modification was achieved with carboxymethyl chitosan. Various characterization techniques were employed to assess the physical and chemical properties of the probe, which were then combined with a CEST contrast agent to investigate the mechanisms of multimodal magnetic resonance imaging and in vitro photothermal effects. Upon integrating the multi-modal molecular probe with Ioversol for imaging purposes, at a magnetic field strength of B 1 = 1.25 μT and with a molecular probe concentration of 0.5 mg/mL, the CEST signal from Ioversol is almost entirely suppressed. This allows for the successful identification of a distinct concentration range where both contrast agents can coexist. In vitro photothermal studies on MXene codoped with iron and manganese have shown that the composite molecular probe exhibits excellent photothermal efficiency. The method combining complex nanoprobes with CEST contrast agents successfully achieved simultaneous imaging of both contrast agents. In vitro MRI experiments successfully obtained distinguishable concentration ranges for both, with changes in CEST signals reflecting the concentration variations of the complex molecular probes, which also exhibit good photothermal therapy (PTT) capabilities.
研究领域:
纳米材料
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磁共振成像
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对比剂
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多模态成像
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光热治疗
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生物医学工程
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材料科学
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PubMed
高影响因子
BIOMATERIALS
·
2012
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IF 7.404
Zhen Liu,Fang Pu,Sa Huang,Qinghai Yuan,Jinsong Ren,Xiaogang Qu
Due to their unique electric, magnetic, and optical properties, engineered nanostructures have been applied to provide diagnostic, therapeutic, as well as prognostic information about the status of disease. In this study, we report a multifunctional nanoprobe based on PEGylated Gd 2 O 3 :Yb 3+ , Er 3+ nanorods (denoted as PEG-UCNPs) for in vivo up-conversion luminescence (UCL), T 1 -enhanced magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. A facile and large-scale hydrothermal system combining the merits of an in situ thermal decomposition method and a surface-modified approach is introduced to construct high-quality PEG-UCNPs. By grafting PEG molecules on the surface of PEG-UCNPs, the nanostructures possess excellent stability against in vivo environment and hold long blood circulation time. Cell-cytotoxicity assay, hemolyticity, as well as post-injection histology, hematology, and inflammation analysis further demonstrate their non-cytotoxic character and indicate further in vivo application. In detail, the capability of PEG-UCNPs as high-performance contrast agents for UCL/MR/CT imaging is evaluated successfully through small-animal experiments. Additionally, pharmacokinetics, biodistribution, and clearance route are studied after intravenous injection in a mouse model, reflecting their overall safety.
研究领域:
纳米技术
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材料科学
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生物医学工程
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医学影像
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分子诊断
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DOI
PubMed
高影响因子
BIOMATERIALS
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2018
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IF 8.806
Xuan Mei,Wei Wang,Liang Yan,Tingting Hu,Ruizheng Liang,Dan Yan,Min Wei,David G. Evans,Xue Duan
Recently, theranostic has drawn tremendous attention by virtue of the nanotechnology development and new material exploration. Herein, we reported a novel theranostic system by loading Au nanoclusters (AuNCs) and Chlorin e6 (photosensitizer, Ce6) onto the monolayer nanosheet surface of Gd-doped layered double hydroxide (Gd-LDH). The as-prepared Ce6&AuNCs/Gd-LDH exhibits a largely enhanced fluorescence quantum yield (QY) of 18.5% relative to pristine AuNCs (QY = 3.1%) as well as superior T 1 magnetic resonance imaging (MRI) performance ( r 1 = 17.57 mM −1 s −1 ) compared with commercial MRI contrast agent (Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA): r 1 ≈ 3.4 mM −1 s −1 ), resulting from a synergistic effect between AuNCs and Gd-LDH. In addition, both in vitro and in vivo therapeutic evaluations demonstrate an efficient dual-modality imaging guided anticancer performance, especially the synergetic enhanced magnetic resonance/fluorescence (MR/FL) visualization of tumor site. Therefore, this work demonstrates a successful paradigm for the design and preparation of LDHs monolayer-based theranostic material, which holds great promises in practical applications.
研究领域:
纳米技术
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材料科学
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癌症治疗
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医学成像
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诊疗一体化
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产品关联
DOI
PubMed
高影响因子