JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 7.3
Weiyuan Xu,Xinjian Ye,Min Wu,Xin Jiang,Lik Hang Hugo TSE,Yanjuan Gu,Kun Shu,Liuhui Xu,Yong Jian,Gengshen Mo,Jiao Xu,Yinghui Ding,Ruonan Gao,Jianliang Shen,Fangfu Ye,Zhihan Yan,Lixiong Dai
The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.
研究领域:
医学影像学
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分子生物学
·
化学
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PubMed
高影响因子
STAR Protocols
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2022
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IF 0
Qingbin Zeng,Qianni Guo,Yaping Yuan,Lei Zhang,Weiping Jiang,Yuqi Yang,Xin Zhou
Summary Due to limited detection sensitivity and contrast limitation, imaging substrates with 129 Xe MRI in living cells is still a challenge. Here, we present an effective protocol to detect and image substrates in human lung cancer cells A549 with hyperpolarized 129 Xe MRI. This protocol was optimized for a cryptophane-based probe sensitive to biothiols and can be expanded to other Xe-based probes to detect potential biomarkers in other mammalian cells. For complete details on the use and execution of this protocol, please refer to Zeng et al. (2021) .
研究领域:
医学成像
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生物医学工程
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分子生物学
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癌症研究
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DOI
PubMed
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 23
·4119-4129
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IF 4.872
Xiaolong Liu,Xinyi Lin,Ming Wu,Ruhui Lin,Buhong Li,Jingfeng Liu
Considerable efforts have been made to incorporate both diagnostic and therapeutic functions into a single nanoplatform for biomedical applications. Herein, we report the synthesis and characterization of magnetite-loaded polymeric micelles (referred as SCDP-LA) for targeted magnetic resonance imaging (MRI) and photothermal therapy of hepatocellular carcinoma (HCC), by using an amphiphilic biocompatible polymer of lactobionic acid-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG-LA) for the micelle formation. A cluster of SPION@Cu2−xS is densely encapsulated inside the hydrophobic core of the micelles, which offers both highly sensitive MRI and an excellent photothermal effect. The LA-modified PEG outlayer makes this micelle stable in aqueous solution. Due to the targeting ligand of LA, the SCDP-LA clusters could be selectively internalized into the hepatocellular cell line (HepG2 cells) but not into HeLa cells. In addition, the targeted ability of the SCDP-LA aqueous solution was further confirmed by enhanced MRI with a shorter T2 relaxation time in HepG2 cells. Meanwhile, it also demonstrates excellent performance to produce significantly enhanced local photothermal killing efficiency against HepG2 cells under NIR laser irradiation. In summary, the present multifunctional nanoplatform based on SPION@Cu2−xS nanoclusters will be a promising theranostic platform for targeted MRI-guided photothermal therapy.
研究领域:
生物医学工程
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肿瘤学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Haitao Huang,Tao Yue,Ke Xu,Jafar Golzarian,Jiahui Yu,Jin Huang
Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd 3+ from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5 nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100 nm and a longitudinal relaxivity ( r 1 ) of 10.2 mM −1 S −1 . Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T 1 -weighted MRI diagnosis of tumor.
研究领域:
生物医学工程
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影像医学
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材料科学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Meilin Shi,Fengmei Zuo,Yingkai Tao,Yawen Liu,Jiahui Lu,Shaohui Zheng,Jiao Lu,Pingfu Hou,Jingjing Li,Kai Xu
Breast cancer is a refractory malignancy particularly in women, with an accruing morbidity and mortality worldwide. The purpose of this study was to evaluate the efficacy of laser-induced near-infrared (NIR) PFP/Gd-DTPA/ICG@PLGA NPs (PGINPs) in US/MR imaging and regimen for breast cancer; gadolinium-DTPA (Gd-DTPA), perfluoropentane (PFP) and indocyanine green (ICG) were wrapped in the poly (lactic-co-glycolic) acid (PLGA) shell membrane via a double emulsion approach. In this study, under the irradiation of NIR laser, the ICG enriched in the cancerous tissue not only converted optic energy into thermal energy to rapidly heat up the cancer focus but also convert O 2 to singlet oxygen ( 1 O 2 ), which can effectively destroy the cancer tissues through photothermal therapy (PTT) and photodynamic therapy (PDT). Meanwhile, the thermal energy thus generated could promote the gasification of PFP to enable visualization of cancer tissues under US imaging. Gd-DTPA in combination with US imaging can also significantly enhance MR imaging to provide US/MR dual-modal imaging. This study proves the efficacy of NIR-inspired multifunctional nano-system PGINPs to potentiate US/MR imaging and regimen for breast cancer.
研究领域:
肿瘤学
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医学影像学
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纳米医学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2016
·Vol. 4
·期 45
·7241-7248
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IF 4.872
Qin Zhu,Heng Yang,Yuanyuan Li,Yu Tian,Wei Wang,Weijun Tang,Yuan Yuan,Aiguo Hu
HP-DO3A-based cationic amphiphilic Gd(III) complexes bearing quaternary ammonium salts of different alkyl chain lengths were synthesized. The structures of the intermediates, the ligands and the Gd(III) complexes were characterized by 1H NMR, 13C NMR, ESI and MALDI-TOF mass spectrometry. Relaxation studies of the amphiphilic Gd(III) complexes revealed that long alkyl chains facilitated the formation of micelles in an aqueous solution and afforded high relaxivity. Electrostatic self-assembly of the GdL1 complex with polyacrylate sodium (PAAS) showed significant relaxation enhancement with the relaxivity being up to 20.03 mM−1 s−1 at 1.5 T, which was about 4 times that of the commercial MRI contrast agent, Gd-DTPA. The long hydrophobic chain was found to play an important role in the formation of the self-assembly. Zeta potential and dynamic light scattering measurements were carried out to reveal the aggregation process during the assembly. Good biocompatibility of the complexes and high cell viability were found in HepG-2 and L-02 cells by the MTT assay. The reactive oxygen species (ROS) generation study further confirmed the biocompatibility. In vivo imaging showed significant contrast enhancement in the liver and bladder regions.
研究领域:
医学影像学
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材料科学
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生物化学
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DOI
PubMed
高影响因子
NMR IN BIOMEDICINE
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2026
·Vol. 39
·期 4
·e70249
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IF 2.8
Xiaomin Duan,Longyang Xiao,Haichen Zhao,Yuanxiang Gao,Lili Wang,Haiyang Yu,Xiaoyuan Zhou,Xiaojuan Shi,Zhiming Li
This study aimed to validate the feasibility of hypoxia-targeted magnetic resonance imaging (MRI) molecular probe (CAIX-Gd) for evaluating hypoxia status in rats with hepatic fibrosis. A macrocyclic ligand compound (Compound 3) was synthesized using the carbonic anhydrase IX (CAIX) inhibitor acetazolamide as the targeting moiety, and its structure was confirmed by 1 H-NMR spectroscopy. CAIX-Gd was then prepared by chelating gadolinium, with free gadolinium content quantified via the xylenol orange assay. In biocompatibility tests, CAIX-Gd administration showed no significant histopathological changes compared with saline controls. For hypoxia detection, rats were divided into three groups: (A) hepatic fibrosis (HF) with CAIX-Gd, (B) HF with DTPA-Gd, and (C) normal controls (NC) with CAIX-Gd. The difference in T1 relaxation time (∆T1) pre- and post-contrast was measured in regions of interest (ROI). HF rats showed increased collagen deposition (Masson staining), α-SMA activation, and elevated hypoxia markers (PIMO/HIF-1α) compared to controls (all p < 0.05). In group C, mild ∆T1 shortening was seen at 10 min post-injection. While ∆T1 continuously decreased in group B, the shortening was significantly greater in group A ( p < 0.05), peaking at 10 min. In conclusion, the CAIX-Gd probe was successfully synthesized and demonstrated potential for the non-invasive MRI detection of hypoxia in hepatic fibrosis.
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2026
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IF 7.8
Xinyi Guo,Mengmeng Wang,Danyang Qu,Hao Cui,Jiajing Gong,Qinglin Shen,Yang Han,Xingqi Pan,Zhenbao Liu,Meilin Shi
Sonodynamic therapy (SDT) offers a noninvasive strategy for tumor ablation through ultrasound-activated sonosensitizers that generate reactive oxygen species (ROS); however, its therapeutic efficacy is often limited by tumor hypoxia. Herein, we report the rational design of a multifunctional theranostic nanoplatform, HA-MnO2-TCPP nanoflowers, that integrates active tumor targeting, dual ROS amplification, and magnetic resonance imaging (MRI) guidance for synergistic sonodynamic and chemodynamic therapy. The MnO2 nanoflowers were loaded with the sonosensitizer 4-carboxyphenyl porphyrin (TCPP) and surface-modified with hyaluronic acid (HA). This design enables CD44 receptor-mediated tumor targeting and tumor microenvironment-responsive degradation. Upon exposure to the mildly acidic and reductive tumor microenvironment, MnO2 is reduced to Mn2+, leading to glutathione depletion, in situ oxygen generation, and alleviation of hypoxia, while the released Mn2+ catalyzes Fenton-like reactions to generate highly toxic hydroxyl radicals (•OH) and simultaneously serves as an efficient T1-weighted MRI contrast agent. Meanwhile, TCPP enhances singlet oxygen (1O2) generation upon ultrasound activation, enabling effective sonodynamic therapy. Through the coordinated activation of SDT and CDT under MRI guidance, HA-MnO2-TCPP nanoparticles achieve precise and efficient tumor suppression without reliance on photothermal mechanisms. This work provides a robust paradigm for tumor microenvironment-responsive nanotheranostics and highlights the potential of ultrasound-activated strategies for precision cancer therapy.
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2026
·
IF 8.7
Dandan Wang,Wenyi Zhang,Lin Chen,Yunxiao Mai,Haoran Wang,Zhenwei Miao,Yang Zhao
Purpose Gadolinium-based contrast agents (GBCAs), which are indispensable for magnetic resonance imaging (MRI), carry a severe risk of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD), particularly in those with advanced renal impairment. This critical safety concern necessitates the development of biocompatible alternatives that do not compromise diagnostic efficacy.Materials and Methods Inulin-based nanoparticles (Inulin@Gd/Zn NPs) were synthesized by chelating inulin with gadolinium and zinc ions, aimed at being used as contrast agents that can replace conventional GBCAs. The morphology, size, and zeta potential of the nanoparticles were determined. The anti-fibrotic ability of Inulin@Gadolinium/zinc nanoparticles (Inulin@Gd/Zn NPs) was evaluated in vitro and in vivo, as well as their MRI imaging ability and metabolic performance in normal and fibrotic kidneys. A unilateral ureteral obstruction (UUO) model was created in mice and was used to evaluate the in vivo anti-fibrotic efficacy.Results The ultra-small Inulin@Gd/Zn NPs (<10 nm) exhibited high stability and T1 relaxivity. Compared to Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), Inulin@Gd/Zn NPs demonstrated precise kidney targeting, excellent T1-weighted MRI capabilities, and rapid renal clearance. In vitro studies showed that Inulin@Gd/Zn NPs had very low cytotoxicity for HK-2 cells up to 100 µM. Further, the NPs were able to reduce reactive oxygen species generation in hydrogen peroxide–stimulated HK-2 cells. Negligible levels of hemolysis and organ toxicity were confirmed in vivo. Further, in the UUO model, administration of Inulin@Gd/Zn NPs was found to significantly inhibit fibrosis. Both in vitro and in vivo experiments demonstrated that Inulin@Gd/Zn alleviated GBCA-induced early tubulointerstitial fibrosis by inhibiting the transforming growth factor-β1 (TGF-β1) signaling pathway.Conclusion Inulin@Gd/Zn NPs represent a promising strategy for clinical application of GBCAs. It addresses the diagnostic and therapeutic challenges in patients with CKD, offering a paradigm shift in the safe application of GBCAs in high-risk populations, indicating the need for further clinical trials to enable clinical applications.
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DOI
PubMed
高影响因子
Applied Materials Today
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2022
·
IF 8.663
Ying Liu,Weiqiang Lin,Fang Yang,Tianfeng Chen
Tumor hypoxic microenvironment is a crucial bottleneck limiting its clinical therapeutic efficacy. Therefore, how to design nano-drugs with clear structure and function based on the characteristics of the tumor microenvironment to overcome the hypoxia of tumors and achieve high-efficiency and low-toxicity treatment is an important strategy to solve the problem of tumor treatment. Herein, we design and synthesize a ternary nano-platform, Ce6-AuCeFe, with longan structure by a simple method to obtain Magnetic Resonance Imaging (MRI)-guided cascade reagent to enhance cancer Photodynamic therapy (PDT). The AuCeFe was synthesized via a one-pot reaction with controlled morphology and loaded with Ce6 to assist PDT. Ce6-AuCeFe was synthesized as a hybrid nanocatalyst model of glucose oxidase and peroxidase mimics because of its outstanding catalytic performance. As nontoxic glucose was continuously converted to abundant H 2 O 2 by AuCeFe, the excess H 2 O 2 was subsequently catalyzed by the peroxidase-like activity of AuCeFe to generate O 2 , which helped to alleviate the hypoxic tumor microenvironment. The mechanistic studies elucidate that the ternary nanoparticles facilitate triplet oxygen into singlet oxygen through energy transfer, which leads to highly toxic reactive oxygen species (ROS) production combined with PDT, achieving much desirable cancer cells killing effect under hypoxia conditions. Meanwhile, the degradation of Ce6-AuCeFe under tumor microenvironment also enhanced on T 1 and T 2 -weighted MRI, indicating that Ce6-AuCeFe could be used as two-mode MRI contrast agents for precisely guiding in therapy. In summary, our study provides a novel strategy for tumor therapy by utilizing well-structured metal composites to achieve high-efficiency oxygen production, thereby overcoming the hypoxic tumor microenvironment.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Shuang Liu,Hewen Li,Yuhang Ding,Dengyi Duan,Lin Cao,Kangkang Liu,Wenyi Zhang,Shifeng Cheng,Yiming Li,Yunfei Guo,Xiang Qi,Jianmin Li,Xuening Zhang,Jing Peng,Gang Han,Yang Zhao
Ferroptosis is triggered by iron-dependent lipid peroxidation, which shows great potential in tumor therapy. However, its biomedical applications are constrained by suboptimal therapeutic efficacy, leakage of metal ions from inducing agents, and the absence of noninvasive evaluation methods. In this study, we aimed to develop a self-reducing nano-theranostic agent (Fe@AP-SAS/RGD, FASR) for tumor-targeted ferroptosis therapy and conducted real-time magnetic resonance imaging(MRI) to monitor ferroptosis by encapsulating iron oxide particles in natural apple pectin (AP). In a weakly acidic tumor microenvironment, the strong reducing ability of AP accelerated the transformation of Fe 3+ within FASR into highly active Fe 2+ . Subsequently, the concentration of Fe 2+ increased and boosted the antitumor effect of ferroptosis. Notably, MRI of prostate cancer mouse models after intravenous injection of FASR NPs at varying doses revealed that the T 2 value decreased at the tumor sites and exhibited a linear correlation with the changes in ferroptosis hallmark markers, tumor weight, and volume after treatment. These findings demonstrate the capacity of T 2 mapping to quantitatively evaluate ferroptosis efficacy. This study not only introduced a tumor-targeted and self-reducing strategy to amplify ferroptosis but also pioneered a novel pathway for noninvasive imaging and monitoring of ferroptosis treatment processes within live tumors.
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2026
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IF 4.4
Liu Yating,Zeng Jie,Yang Xianghua,Chen Ziyan,Sun Wang,Tan Shuo,Chen Feng,Zhao Zhenghuan,Zhao Xinyu
Although traditional cancer therapy is widely used, it still faces treatment and some serious adverse reactions. This study developed an “all-in-one” multifunctional nanotherapeutic agent that integrates the dual capabilities of magnetic resonance imaging (MRI) and photothermal/chemodynamic therapy (PPT/CDT). In brief, a multifunctional nanotherapeutic agent was successfully synthesized for MRI and photothermal/chemodynamic therapy by modifying a manganese gallate complex with dopamine (Mn-GA@PDA NPs). We found that at a concentration of 400 μg/mL of Mn-GA@PDA NPs and under irradiation with near-infrared light at 1.5 W/cm 2 for 10 min, the temperature could rapidly rise to 59 ℃. Moreover, the cell survival rate was much lower than that of the group without laser irradiation. In the animal experiment, a significant difference between the Mn-GA@PDA NPs + NIR group and the PBS group. The antitumor effect was 9.5 times that of the PBS group. The in vitro and in vivo experiments demonstrated that the Mn-GA@PDA NPs, possessing chemodynamic and photothermal activity, inhibited the growth of breast cancer 4T1 cells. Due to the inherent high paramagnetism of manganese ion, the Mn-GA@PDA NPs effectively accelerate the longitudinal relaxation rate under normal physiological conditions, demonstrating certain T1-weighted magnetic resonance imaging ability. The calculated molar longitudinal relaxation rate was r 1 = 4.4 mM −1 s −1 , providing robust support for precision medicine. Our Mn-chelating nanoplatform is a promising MRI–visible theragnostic agent for synergistic cancer combination therapy.
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高影响因子
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