查找使用阿拉丁产品的科研文献

Iron-doped Zif-8 nanoplatform for MRI-guided synergistic microwave thermal/chemodynamic therapy of triple-negative breast cancer

Zhenyu Xiang,Jialing Liu,Yan Zhang,Ru Shen,Ying Lu,Rong Li,Qinying Shi,Guannan Zhang,Sijin Li,Jianbo Song

Triple-negative breast cancer (TNBC), a highly refractory malignancy characterized by aggressive clinical behavior, poses a significant therapeutic challenge due to its resistance to conventional treatments. While microwave thermal therapy (MWTT) emerges as a promising modality for TNBC treatment through deep-tissue penetration and uniform energy delivery, its reliance on prolonged hyperthermia exposure risks collateral damage to adjacent healthy tissues. Herein, we present a rationally engineered iron-doped zeolitic imidazolate framework-8 nanoplatform (Fe@Zif-8). This study aimed to develop a theranostic agent for MRI-guided combination therapy by pursuing the following objectives: (1) synthesizing and characterizing Fe-doped ZIF-8; (2) evaluating the enhancement of microwave thermal conversion efficiency via iron doping; (3) validating the nanoparticle's Fenton catalytic activity for reactive oxygen species (ROS) generation and glutathione depletion in the tumor microenvironment; and (4) demonstrating the synergistic antitumor efficacy of combined MWTT and CDT both in vitro and in vivo . Accordingly, Fe@Zif-8 was synthesized via a one-pot solvothermal method and systematically characterized. Its therapeutic performance was then rigorously assessed through a series of physicochemical and biological experiments. The iron dopants substantially enhance microwave absorption and dielectric loss effects in Zif-8 matrices, enabling Fe@Zif-8 to generate intensified hyperthermia under MW irradiation. Concurrently, iron ions released from the nanoplatform react with endogenous hydrogen peroxide (H 2 O 2 ) via Fenton catalysis to produce substantial ROS. The concerted action of MWTT and CDT achieves rapid tumor ablation while significantly reducing therapeutic energy requirements. Furthermore, the platform served as an effective T2 contrast agent for magnetic resonance imaging (MRI), enabling non-invasive monitoring. This work provides a new approach for the preparation of nanomaterials with highly efficient anti-TNBC performance.

A Copper(I)-Azurin complex suppresses p53-mediated glycolysis to sensitize breast cancer to cuproptosis with MRI monitoring

Hui Wang,Yu Zhang,Dinghua Liu,Chang Liu,Shuang Wu,Zhuoyao Wu,Tianming Cui,Gongyao Yu,Yan Xu,Weitao Yang,Bingbo Zhang

The Warburg effect drives cancer cells to rely preferentially on glycolysis, resulting in diminished mitochondrial oxidative phosphorylation (OXPHOS). This metabolic phenotype limits the ability of excess copper (Cu) ions to trigger cuproptosis in dysfunctional mitochondria, leading to suboptimal therapeutic outcomes. Therefore, remodeling tumor energy metabolism to counteract the Warburg effect represents a pivotal strategy to enhance cuproptosis efficacy. Herein, we developed a Cu(I)-stabilized metal-organic framework nanoplatform (CuTz-1) encapsulated by Azurin (CuTz-1@Azurin) as a cuproptosis sensitizer. Mechanistically, Azurin increases p53 protein levels by intercepting MDM2-mediated ubiquitin-proteasome degradation. Elevated p53 subsequently inhibits pyruvate kinase M2 (PKM2) activity, suppressing glycolysis, while simultaneously promoting mitochondrial OXPHOS—collectively shifting cellular metabolism from glycolysis toward mitochondrial respiration and sensitizing tumor cells to Cu-induced proteotoxic stress. In addition, CuTz-1@Azurin triggers oxidative stress via reactive oxygen species (ROS) generation and glutathione (GSH) depletion, which act together with p53-mediated apoptosis to suppress tumor growth. Meanwhile, the oxidation of Cu(I) to paramagnetic Cu(II) enables real-time monitoring of the therapeutic process by magnetic resonance imaging (MRI). Both in vitro and in vivo results demonstrate good antitumor performance of CuTz-1@Azurin. This study highlights the potential of Azurin-mediated metabolic regulation as a promising strategy to potentiate cuproptosis for combined cancer therapy.

Synergic fabrication of hybrid nanocapsules gold-organosilica for MRI-guided photothermal-enhanced synergistic effect chemodynamic lung cancer therapy

Dongdong Wang,Na Xu,Yang Guo,Dan Wang,Yongqiang Liang

A dual-mode T1 MRI/CT contrast agent of Gd2O3/Au@MSNs for tumor imaging with high performance

Jianfeng Yang,Qingling Zhao,Zehao Zang,Shuquan Zhang,Ziwu Wang,Lanlan Li,Xiaofei Yu,Xiaojing Yang,Zunming Lu,Xinghua Zhang

Magnetic resonance imaging (MRI) contrast agents with high relaxivity is of great importance for clinical diagnosis. Here we propose an effective method to enhance the relaxivity of MRI contrast agents. Ultra-small gadolinium oxide nanoparticles (Gd 2 O 3 NPs) with different surface ligands were prepared by coprecipitation method, and the polyacrylic acid (PAA) modulated Gd 2 O 3 NPs (PAA-Gd 2 O 3 ) have the high r 1 relaxivity of 53.34 mM –1 s –1 , which is mainly induced by the strong affinity between PAA and water molecules. In addition, PAA modulated Gd 2 O 3 NPs were successfully loaded on Au@MSNs (Au nanorod coated with mesoporous silica , Gd 2 O 3 /Au@MSNs) with enhanced affinity between Gd 3+ and water molecules, as well as increased motional time of Gd 3+ . Therefore, the r 1 relaxivity of Gd 2 O 3 /Au@MSNs can be up to 64.53 mM –1 s –1 , which is 17 times of the commercial agent Gd-DTPA. The Gd 2 O 3 /Au@MSNs NPs also have a low r 2 /r 1 of 1.04 and good computed tomography (CT) imaging performance, as well as good biocomatibility, which have great potential applications in multimodal bioimaging.

A collagenase-decorated Cu-based nanotheranostics: remodeling extracellular matrix for optimizing cuproptosis and MRI in pancreatic ductal adenocarcinoma

Wang Yining,Zhou Qiaomei,Luo Wangping,Yang Xiaoyan,Zhang Jinguo,Lou Yijie,Mao Jin,Chen Jiayi,Wu Fan,Hou Jue,Tang Guping,Bai Hongzhen,Yu Risheng

Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers.Graphical Abstract

“Two-in-One” Fabrication of Fe3O4/MePEG-PLA Composite Nanocapsules as a Potential Ultrasonic/MRI Dual Contrast Agent

Bin Xu,Hongjing Dou,Ke Tao,Kang Sun,Jing Ding,Weibin Shi,Xiasheng Guo,Jiyu Li,Dong Zhang,Kun Sun

A new method for the fabrication of Fe3O4 nanoparticles enveloped by polymeric nanocapsules is proposed. This method is characterized by combining a double emulsification with the interfacial coprecipitation of iron salts to form Fe3O4/polymer composite nanocapsules in a single step. To demonstrate the viability of this approach, methoxy poly(ethylene glycol)-poly(lactide) (MePLEG) was chosen as the shell material for Fe3O4/MePLEG nanocapsules. In addition to the versatility offered for fabricating nanocapsules with different shell materials, the method was found to be convenient for adjusting the magnetite content of the nanocapsules from 0 to 43%. In addition to their confirmed T2-weighted magnetic resonance imaging (MRI) enhancement, the resultant composite nanocapsules display much more obvious acoustic responses than MePLEG nanocapsules in an acoustic investigation. Furthermore, the low toxicity of these composite nanocapsules, as confirmed by our study, combined with their magnetic and acoustic properties ensure that these composite nanocapsules have great potential in acting as ultrasonic/MRI dual contrast agents.

Folic acid-modified Prussian blue/polydopamine nanoparticles as an MRI agent for use in targeted chemo/photothermal therapy

Xiao Lin,Yanbin Cao,Jiong Li,Dongye Zheng,Shanyou Lan,Yanan Xue,Faquan Yu,Ming Wu,Xunjin Zhu

Fabricating multifunctional theranostic nanoparticles is highly pursued but still challenging for effective cancer treatment. Herein is reported a new theranostic nanoagent as both an MRI and targeted chemo/photothermal therapeutic agent. Prussian blue nanoparticles (PB) were first decorated with polydopamine (PDA), then conjugated with polyethylene glycol (PEG) and folic acid (FA), and finally loaded with doxorubicin (DOX) (denoted as PB@PDA@PEG-FA-DOX). The nanoagent was estimated to have an average size of 40 nm with a DOX-loading capacity of 36%, photothermal conversion efficiency of 45.7% and a transverse relaxation rate of 0.366 mM−1 s−1. In vitro release investigations showed a dual-responsive release by a mild acid and near-infrared (NIR) laser irradiation. PB@PDA@PEG-FA illustrated negligible cytotoxicity against the HL-7702 cell line and 38.2% cell viability under NIR against the HeLa cell line. PB@PDA@PEG-FA-DOX exhibited 45.2% cell viability. In contrast, the cell viability of PB@PDA@PEG-FA-DOX was dramatically decreased to 18.4% under NIR. Exclusive of folic acid, PB@PDA@PEG-DOX demonstrated 40.5% cell viability. These results demonstrated the potential of the nanoagent for integrated photothermal therapy (PTT) and chemotherapy, also embracing the FA targeting effect. In vivo MRI confirmed the effective nanoparticle accumulation, while infrared thermal images revealed the dramatically increased temperature under NIR at a tumor site. In vivo combination treatment-induced tumors were nearly completely destroyed without significant body weight loss after 14 days. H&E and Ki67 staining indicated remarkable necrosis and weak cell proliferation in the tumor area. Histologic examination revealed a lower toxicity in the vital organs. Therefore, this combination of chemo/photothermal therapy could provide an efficient route for cancer treatment.

Designing highly stable ferrous selenide-black phosphorus nanosheets heteronanostructure via P-Se bond for MRI-guided photothermal therapy

Deng Xuanru,Liu Hongxing,Xu Yuan,Chan Leung,Xie Jun,Xiong Zushuang,Tang Zheng,Yang Fang,Chen Tianfeng

Background The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent.Results Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo.Conclusion sCollectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.Graphic abstract

Exfoliation and in situ functionalization of MoS2 nanosheets for MRI-guided combined low-temperature photothermal therapy and chemotherapy

Lulu Cai,Lina Dong,Xuan Sha,Shuai Zhang,Siwen Liu,Xiaoxi Song,Mingming Zhao,Qi Wang,Kai Xu,Jingjing Li

Traditional photothermal therapy (PTT) usually requires hyperthermia (greater than50 °C) to mediate effective tumor ablation, which could inevitably induce heating damage to the adjacent normal tissues. Therefore, to achieve effective tumor killing at relatively low temperature is crucial to improve the application of PTT. MoS 2 , as an attractive photothermal agents, have attracted much attention in biomedical applications. But the separation of exfoliation and functionalization of MoS 2 nanosheets (NSs) partly complicates the preparation process of MoS 2 NSs-based theranostic nanomaterials. Herein, we formulated a facile one-pot approach for the exfoliation and in situ functionalization of single-layer MoS 2 nanosheets by using bovine serum albumin template gadolinium oxide (BSA-Gd 2 O 3 ) nanoparticles as the exfoliating agent and magnetic resonance imaging (MRI) T 1 contrast agent. On this basis, hyaluronic acid (HA) was further conjugated to target cancer cells with overexpression of CD44, and then gambogic acid (GA), a natural heat shock protein 90 inhibitor and antitumor drug was loaded, which could reduce the thermo-resistance of tumor cells and achieve effective PTT at a mild temperature (43–45 °C). In this research, both in vitro and in vivo experiments have confirmed that the GA/MoS 2 /BSA-Gd 2 O 3 -HA nanocomposite possesses good biocompatibility and is promising for the application in MRI-guided combined low-temperature PTT and chemotherapy.

Extracellular-vesicles delivered tumor-specific sequential nanocatalysts can be used for MRI-informed nanocatalytic Therapy of hepatocellular carcinoma

Han Wu,Hao Xing,Meng-Chao Wu,Feng Shen,Yu Chen,Tian Yang

Background: Conventional therapeutic strategies for advanced hepatocellular carcinoma (HCC) remains a great challenge, therefore the alternative therapeutic modality for specific and efficient HCC suppression is urgently needed. Methods: In this work, HCC-derived extracellular vesicles (EVs) were applied as surface nanocarrier for sequential nanocatalysts GOD-ESIONs@EVs (GE@EVs) of tumor-specific and cascade nanocatalytic therapy against HCC. By enhancing the intracellular endocytosis through arginine-glycine-aspartic acid (RGD)-targeting effect and membrane fusion, sequential nanocatalysts led to more efficient treatment in the HCC tumor region in a shorter period of time. Results: Through glucose consumption as catalyzed by the loaded glucose oxidase (GOD) to overproduce hydrogen peroxide (H 2 O 2 ), highly toxic hydroxyl radicals were generated by Fenton-like reaction as catalyzed by ESIONs, which was achieved under the mildly acidic tumor microenvironment, enabling the stimuli of the apoptosis and necrosis of HCC cells. This strategy demonstrated the high active-targeting capability of GE@EVs into HCC, achieving highly efficient tumor suppression both in vitro and in vivo . In addition, the as-synthesized nanoreactor could act as a desirable nanoscale contrast agent for magnetic resonance imaging, which exhibited desirable imaging capability during the sequential nanocatalytic treatment. Conclusion: This application of surface-engineering EVs not only proves the high-performance catalytic therapeutic modality of GE@EVs for HCC, but also broadens the versatile bio-applications of EVs.

Tumor environment responsive degradable CuS@mSiO2@MnO2/DOX for MRI guided synergistic chemo-photothermal therapy and chemodynamic therapy

Minyi Zhang,Xijian Liu,Qian Luo,Qi Wang,Linjing Zhao,Guoying Deng,Renbin Ge,Lei Zhang,Junqing Hu,Jie Lu

Chemo-photothermal therapy and chemodynamic therapy have a great promise for enhanced tumor treatment effect for integration of Reactive Oxygen Species (ROS) and O 2 generation. Hereby, a smart tumor environment (TME) responsive theranostic agent based on CuS@mSiO 2 @MnO 2 nanocomposites was fabricated by a facile method. When the nanocomposites entered tumor, the drug release was triggered by multi-model response of NIR irradiation, weak acidity and high glutathione (GSH) in TME. The O 2 and toxic •OH were generated from H 2 O 2 in TME through catalyzing by MnO 2 , which relieved hypoxia and enhanced the effect of chemodynamic therapy (CDT). Meanwhile, the generated Mn 2+ in TME was used to monitor the nanocomposites delivery by magnetic resonance imaging (MRI). Also, the excellent photothermal therapy effect could be triggered by NIR irradiation for CuS core. More importantly, the growth of tumors was greatly inhibited by the synergetic chemo-photothermal therapy and CDT. This work may open a wide route for tumor environment responsive theranostic, including relieving hypoxia, chemo-photothermal therapy, CDT and MR imaging.

IL-6-targeted ultrasmall superparamagnetic iron oxide nanoparticles for optimized MRI detection of atherosclerotic vulnerable plaques in rabbits

Huaqiang Mo,Chenxing Fu,Zhiye Wu,Peng Liu,Zhibo Wen,Qingqing Hong,Yanbin Cai,Gongxin Li

Vulnerable plaques of atherosclerosis (AS) are the main culprit lesion for the serious risk of acute cardiovascular disease (CVD). Therefore, developing new non-invasive methods to detect vulnerable plaques and to evaluate their stability effectively is of great value in the early diagnosis of CVD. IL-6 plays a vital role in the development and rupture of AS. In this study, IL-6-targeted superparamagnetic iron oxide nanoparticles (Anti-IL-6-USPIO) are synthesized by a chemical condensation reaction. An AS model was established by damaging rabbit abdominal aortic intima with Foley's tube in combination with a high cholesterol diet. The results confirm that Anti-IL-6-USPIO have excellent IL-6-targeting ability and usefulness in detecting vulnerable plaques in vitro and in vivo, which may provide a novel, non-invasive strategy for evaluating acute cardiovascular risk or exploiting anti-atherosclerotic drugs.