BIOMATERIALS
·
2016
·
IF 8.387
Qiuming Liu,Liwen Song,Shuai Chen,Jingyi Gao,Peiyu Zhao,Jianzhong Du
Improving the relaxivity of magnetic resonance imaging (MRI) contrast agents is an important challenge for cancer theranostics. Herein we report the design, synthesis, characterization, theoretical analysis and in vivo tests of a superparamagnetic polymersome as a new MRI contrast agent with extremely high T 2 relaxivity (611.6 mM −1 s −1 ). First, a noncytotoxic cancer-targeting polymersome is synthesized based on a biodegradable diblock copolymer , folic acid-poly( l -glutamic acid)- block -poly( ε -caprolactone) [FA-PGA- b -PCL]. Then, ultra-small superparamagnetic iron oxide nanoparticles (SPIONs) are in situ generated in the hydrophilic PGA coronas of polymersomes to afford magnetic polymersomes. The in vivo MRI assay revealed prominent negative contrast enhancement of magnetic polymersomes at a very low Fe dose of 0.011 mmol/kg. Moreover, this cancer-targeting magnetic polymersome can effectively encapsulate and deliver anticancer drug to inhibit the tumor growth, demonstrating promising theranostic applications in biomedicine .
研究领域:
生物医学工程
·
纳米医学
·
分子影像学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Zhang Hanyuan,Fang Weijun,Zhao Tingting,Zhang Huabing,Gao Liang,Li Jingya,Wang Rujing,Xu Weiping
The cartilage has poor ability to mount a sufficient healing response. Herein, kartogenin (KGN), an emerging stable non-protein compound with the ability to recruit bone marrow mesenchyme stem cells (BMSCs) to promote chondrogenic differentiation, was grafted onto dopamine-Fe(III) chelating nanoparticles, followed by involving a gelatin- and dextran-based injectable hydrogel to mimic the extracellular matrix to promote cartilage repair. The in vitro results demonstrated that KGN underwent long-term sustained release behavior and availably promoted the deep migration of BMSC cells in yielding hydrogels. Furthermore, in vivo New Zealand white rabbits’ cartilage defect model repairing results showed that cartilage defect obtained significant regeneration post operation in the 12th week, and the defect edge almost disappeared compared to adjacent normal cartilage tissue. Meanwhile, the T2-weighted magnetic resonance imaging (MRI) property resulting from dissociative Fe (III) can significantly monitor the degradation degree of the implanted hydrogels in the defect site. This integrated diagnosis and treatment system gives insight into cartilage regeneration.
研究领域:
生物医学工程
·
再生医学
·
材料科学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yupeng Shi,Mengyang Zhou,Yong Zhang,Yifei Wang,Jingliang Cheng
Image-guided stimulus-responsive theranostics are beneficial for identifying malignant lesions and integrating multiple cell-killing mechanisms to enhance tumor cell clearance. Herein, an intelligent dual-responsive nanostructure (HSPMH-DOX) was developed for magnetic resonance imaging (MRI)-guided synergistic chemo-photothermal therapy (PTT) and chemodynamic therapy (CDT). The core-shell nanostructure was synthesized by layering polydopamine (PDA), manganese oxide (MnO 2 ), and hyaluronic acid (HA) onto drug-loaded hollow mesoporous silica nanoparticles (HS). The constructed nanoagent has both endogenous and external dual responses. The tumor microenvironment (pH/GSH) can trigger the degradation of gatekeeper (MnO 2 and PDA), resulting in the release of anti-tumor drugs, whereas external near-infrared light irradiation can accelerate the degradation process and generate local overheating, resulting in PTT. Notably, MnO 2 can not only consume intracellular GSH to enhance CDT but also release Mn 2+ for precise localization of tumor tissues using MRI. Both in vitro and in vivo experiments showed that the prepared dual-response nanoagent satisfied biocompatibility, targeting, and the great efficiency of MRI-guided combined therapy. In animal models , combining chemo-PTT and CDT can eradicate tumors in less than two weeks. This work could pave the way for a wide range of stimulus-responsive synergistic theranostic applications, including MRI, chemo-photothermal therapy, and chemodynmic therapy. Statement of significance Low bioavailability and severe side effects remain the major limitations of conventional cancer chemotherapy. Image-guided combination therapy can alleviate these problems and improve tumor-specific therapy. In the present study, the anticancer drug doxorubicin was encapsulated in a core-shell hollow mesoporous silica nanostructure (HSPMH-DOX), enabling MRI-guided targeted release under both endogenous and external dual stimuli. Moreover, the photothermal and nanoenzymatic effects of nanomedicine can cause local overheating in the tumor and amplify the intracellular CDT effect, accelerating tumor eradication. Systematic evaluations in vitro and in vivo confirmed that nanomedicine enables highly effective MRI-guided synergistic chemo-photothermal and chemodynamic therapy. This work offers a promising therapeutic strategy for precise anti-tumor applications.
研究领域:
肿瘤学
·
医学影像
·
纳米医学
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DOI
PubMed
高影响因子
Open Life Sciences
·
2022
·Vol. 17
·期 1
·952-959
·
IF 1.311
Lei Xia,Xiaowei Song,Guanghai Yan,Jishan Quan,Guangyu Jin
This study aims to synthesize a magnetic resonance imaging (MRI) contrast agent that can specifically target the asialoglycoprotein receptor of liver cancer cells and evaluate its ability as a targeted MRI contrast agent. Lactobionic acid (LA) and polyethylene glycol (PEG) were used to modify superparamagnetic iron oxide nanoparticles (SPION) to obtain LA-PEG-SPION. LA-PEG-SPION was uniformly spherical under the electron microscope, with regular morphology and good dispersion. The particle size of LA-PEG-SPION was about 30 ± 4.5 nm, and its surface potential was about 31 ± 1.5 mV. LA-PEG-SPION had no toxicity or low toxicity to HepG2 cells and HeLa cells, even at 400 μg/mL. The uptake of LA-PEG-SPION by HepG2 cells was higher than that of SPION, with increased blue-stained particles. The fluorescent labeling rate of HepG2 cells reached 68.8%, which was higher than that of the control group. In vitro, MRI showed that the T2-weighted signal intensity of HepG2 cells was lower than that of the control group. Conclusively, LA-PEG-SPION nanoparticles are synthesized in a simple and efficient way. They are successfully applied to the T2-weighted contrast-enhanced MRI in liver cancer in vitro , and they have the potential to be used for in vivo research and clinical studies.
研究领域:
纳米技术
·
医学影像
·
癌症研究
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2023
·Vol. 16
·期 5
·639
·
IF 4.6
Shaowei Bo,Dong Zhang,Mengjie Ma,Xukai Mo,Julia Stabinska,Michael T. McMahon,Changzheng Shi,Liangping Luo
Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0–4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8–5.0 ppm from water while exchange rates varied from ~680 to 2340 s−1at pH 7.2, which allows strong CEST contrast on scanners down to B0= 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.Keywords:chemical exchange saturation transfer (CEST);acyl hydrazides;acyl hydrazones;cancer diagnosis
研究领域:
医学影像学
·
分子生物学
·
生物医学工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 26
·6147-6158
·
IF 7
Xiaoxi Song,Chun Zhang,Mengyuan Xing,Chunyan He,Dongxu Wang,Lijuan Chong,Xiuli Zhang,Minghui Chen,Jingjing Li
Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
分子影像
·
免疫疗法
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2019
·Vol. 31
·期 6
·065101
·
IF 3.399
Qing-Yi Zhuang,Xiao-Hui Wang,Zhao-Xin Geng,Hong-Shang Peng
In this study, fluorescence-encoded magnetic biocompatible nanoparticles (NPs) were constructed from CdSe@ZnS quantum dots (QDs) and Fe3O4 nanoparticles with a one-step reprecipitation-encapsulation method. The resultant hybrid NPs exhibit small size (∼130 nm in diameter), highly bright QDs, two-color emissions (green and red) under single-wavelength excitation, easy separation with a magnet and efficient cellular internalization. Energy transfer between the incorporated QDs was studied to better tailor the encoded fluorescence, and 11 barcodes were obtained by adjusting the ratio of green and red QDs. We used four sets of the barcodes to tag specific cancer cells (HepG2) as a proof-of-concept, and distinguished each set according to respective overlayed fluorescence images using laser confocal microscopy. Moreover, the incorporated Fe3O4 NPs endowed as-constructed optical barcode superparamagnetic property by T2-enhanced magnetic resonance effect with an r2 value of 145.25 s−1 mM−1 at 3 T. These results suggest that the multifunctional NPs are very promising for discriminating different cells and dual-modality imaging.
研究领域:
生物医学工程
·
纳米医学
·
分子影像学
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DOI
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Lin Gao,Lisi Xie,Xiaojing Long,Zhiyong Wang,Cheng-Yi He,Zhi-Ying Chen,Lei Zhang,Xiang Nan,Hulong Lei,Xin Liu,Gang Liu,Jian Lu,Bensheng Qiu
Gene therapy is a very promising technology for treatment of liver diseases. Minicircle DNA (MCDNA) is a versatile gene vector , which possesses excellent features in bio-safety and duration of transgene expression. However, its application has been hampered by the lack of an efficient gene delivery system . In this study, we developed a magnetic resonance imaging (MRI) visible nanoparticle to monitor MCDNA gene delivery and explore the potential of gene therapy in vivo . The nanoparticle was constructed via self-assembly of stearic acid modified low molecular polyethyleneimine (stPEI) and superparamagnetic iron oxide (SPIO) nanocrystals . The multiple SPIO nanocrystals with a controlled clustering structure in the nanoparticles were designed to achieve high MRI sensitivity. Furthermore, the MCDNA was combined with the nanoparticles via electronic interaction. Through intrabiliary infusion, the stPEI-SPIO/MCDNA nanoparticles were efficiently delivered to liver that was visualized by MRI in vivo and confirmed by histology. Moreover, the MCDNA nanoparticles exhibited non-cytotoxicity with no obvious inflammation in the transfection sites. These results indicate that stPEI-SPIO nanoparticle is able to serve as both an efficient DNA vector delivery system and a sensitive agent for MRI visualization.
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DOI
PubMed
高影响因子
Science of Advanced Materials
·
2019
·Vol. 11
·期 6
·893-901
·
IF 1.158
Zhang Zhongtao,Zhang Guangkun,Ji Jingtian,Gao Zhonghui
Nuclear magnetic resonance imaging (MRI) has high image resolution and is widely used in the medical field, but it has the problem of inadequate sensitivity. Therefore, contrast material is needed to enhance the image clarity and accuracy of MRI. In order to further improve the cell
resolution of magnetic resonance imaging (MRI), a new contrast agent, BaYbF5/BaGdF5-Tm, Yb, is obtained by using BaYbF5 and BaGdF5 as the main raw materials and using high temperature thermal decomposition method. A layer of polyethylene glycol (PEG) is added to the material
from the point of view of biocompatibility. TEM and XRD are used to characterize the material, and MTT is used to test the cytotoxicity of the material. The material is used in the imaging process of stem cell-Danhong in the treatment of cerebral infarction. Bioluminescence imaging, immunofluorescence
testing and autoradiography are carried out. A large number of tests have confirmed that the material has low cytotoxicity and is similar to the existing contrast agents in MRI imaging. In bioluminescent imaging experiments, using BaYbF5/BaGdF5-Tm, Yb contrast agent can enhance the optical
density of imaging. In autoradiography test, using BaYbF5/BaGdF5-Tm, Yb contrast agent can clearly show the changes of various tissues. In immunofluorescence test, using BaYbF5/BaGdF5-Tm, Yb contrast agent can find more vascular proliferation cells survive. The new contrast agent proposed
in this study can enhance the imaging ability of MRI. Compared with conventional contrast agents, it has higher cell resolution and lower cytotoxicity. It has positive significance for future disease detection in medicine.
研究领域:
医学影像学
·
神经病学
·
材料科学
·
生物医学工程
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DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2025
·
IF 3.9
Simin Chen,Guizhen Xu,Xiao Li,Yixian Peng,Yuanfang Feng,Jianqiong Pan,Qingao Meng,Shanni Hong,Xiahui Lin
The tumor microenvironment (TME) exhibits metabolic dysfunction characterized by lactate (LA) accumulation, which leads to tumor progression, angiogenesis, and therapy resistance. Targeting LA metabolism through lactate oxidase (LOX) converting LA to pyruvate and hydrogen peroxide (H2O2) under aerobic conditions is a promising therapeutic strategy. However, LOX activity is limited by TME hypoxia. To overcome this limitation, we developed an integrated nanotheranostic system based on hollow MnO2 nanoparticles loaded with LOX and cinnamaldehyde (CA) and modified with hyaluronic acid (HA) for tumor-targeted delivery (denoted as MCLH). In the acidic TME, MCLH decomposes to release LOX and CA, while MnO2 reacts with endogenous H2O2 to generate O2. The resulting O2 maintains LOX-mediated LA oxidation, thereby providing additional H2O2 to promote further O2 production, establishing a self-sustaining cycle that continuously consumes lactate. Meanwhile, CA depletes glutathione via Michael addition, disrupting redox homeostasis and enhancing H2O2 accumulation to increase oxidative stress. The released manganese ions (Mn2+) also enable magnetic resonance imaging (MRI) contrast for real-time monitoring. These cascading effects collectively achieve the synergistic regulation of LA metabolism and oxidative damage, providing an effective strategy for tumor treatment.
研究领域:
纳米医学
·
癌症治疗
·
分子影像学
·
活性氧生物学
·
肿瘤代谢
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2026
·
IF 7.3
Zhou Xiang,Wu Wanjia,Deng Zilong,Liu Hao,Liu Ningxuan,Lu Jiajia,Zheng Xiaoting,Wen Yukang,Lv Sike,Zhou Lin,Zhang Nan,Zhao Peng,Lin Bingquan,Tao Jia
Gadolinium (Gd)-based magnetic resonance imaging (MRI)
contrast
agents (CAs) suffer from limitations including rapid renal clearance
and potential biological risks, highlighting the urgency to develop
safer and more efficient alternatives. Herein, we report a novel Mn(II)-based
MRI CA (Mn@nPFC-1) constructed by loading Mn 2+ ions into
a nanoscale hydrogen-bonded organic framework (nPFC-1), which is self-assembled
from 1,3,6,8-tetra( p -benzoic acid)pyrene (H 4 TBAPy). The Mn@nPFC-1 exhibits high stability benefiting from its
integration of hydrogen bonding and π–π stacking
interactions between the building blocks. In-vitro MRI tests under
3.0 T scanner show that Mn@nPFC-1 exhibits a high longitudinal relaxation
rate ( r 1 = 7.40 mM –1 ·s –1 ), which is significantly superior to
the clinically approved MnDPDP and clinical used Gd-based CAs. Fast
field cycling nuclear magnetic resonance (FFC-NMR) reveals that the
enhanced relaxation performance arises from the restricted rotational
motion of Mn 2+ and the prolonged rotational correlation
time. In-vivo studies across multiple tumor models demonstrate that
Mn@nPFC-1 enables effective T 1 -weighted
MRI contrast enhancement; it can further detect ultrasmall tumors
(3.29 mm 3 ) and assist in accurate MRI-guided tumor resection.
This work provides a promising strategy for designing biosafe, high-performance
Mn-based MRI CAs using hydrogen-bonded organic frameworks as carriers,
holding great potential for clinical tumor diagnosis and image-guided
therapy.
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Shuai He,Fulin Li,Pan Yang,Yanying Sun,Jian Chen,Jingyi Gao,Mingdong Xu,Liguo Hao
Dense stromal barriers and lysosomal sequestration severely restrict the extracellular transport and intracellular trafficking of nanomedicines in pancreatic cancer, while the robust glutathione (GSH)-dependent antioxidant defense further compromises therapeutic efficacy. Here, we developed a proton sponge-enabled dual-driven nanomotor, HA/PEI-DOX@MMSN@Pt (HPDMP), for MRI-guided pancreatic cancer therapy. The asymmetric Pt domain generated near-infrared (NIR)-induced self-thermophoretic motion as the principal externally controllable driving mechanism, whereas endogenous H 2 O 2 provided auxiliary catalytic propulsion, together facilitating nanomotor transport through the dense tumor stroma and enhancing intratumoral penetration. Following cellular uptake, PEI-mediated proton sponge activity facilitated lysosomal escape and increased cytosolic DOX availability. Meanwhile, tumor-microenvironment-responsive degradation of the Mn-doped framework consumed GSH and released Mn 2+ , thereby enhancing reactive oxygen species (ROS) generation, ferroptosis-associated oxidative damage, and T 1 -weighted MRI contrast. HA modification further promoted CD44-mediated tumor targeting. Under NIR irradiation, HPDMP achieved pronounced antitumor efficacy with favorable biosafety. This work provides a barrier-oriented nanomotor strategy for pancreatic cancer therapy.
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DOI
高影响因子
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