Materials Today Bio
·
2026
·
IF 11
Pan Yang,Shuai He,Mingdong Xu,Yanying Sun,Jingyi Gao,Jian Chen,Tongtong Niu,Liguo Hao
Pancreatic cancer responds poorly to conventional chemotherapy, largely because of the pronounced resistance of tumor cells to chemotherapy-induced apoptosis. Ferroptosis, a non-apoptotic form of programmed cell death, has emerged as a promising strategy to overcome this resistance. However, its therapeutic efficacy is often limited by insufficient hydrogen peroxide (H 2 O 2 ) and excessive glutathione (GSH) in the tumor microenvironment (TME). Herein, we developed a nanoplatform, HM-MnO 2 @DOX/CaO 2 @PDA/HA (HMDCPH), using hollow mesoporous manganese dioxide (HM-MnO 2 ) as a carrier to co-deliver doxorubicin (DOX) and calcium peroxide (CaO 2 ). The crosslinked PDA/HA shell enhanced both the tumor-targeting capability and biocompatibility of the nanoplatform. In the TME, HM-MnO 2 depleted GSH and promoted reactive oxygen species (ROS) generation, whereas CaO 2 decomposition generated H 2 O 2 and released Ca 2+ , inducing mitochondrial calcium overload and further aggravating oxidative stress. These synergistic effects enhanced lipid peroxidation (LPO) and exacerbated ferroptosis-related oxidative damage. Moreover, the near-infrared (NIR)-triggered photothermal effect further strengthened the antitumor efficacy of HMDCPH. In addition, nanoplatform degradation released Mn 2+ , enabling T 1 -weighted magnetic resonance imaging (MRI). Collectively, this study presents a synergistic nanotherapeutic strategy that integrates chemotherapy, photothermal therapy, and ferroptosis-related mechanisms to overcome chemoresistance in pancreatic cancer.
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Wenjun Le,Zeyi Sun,Tieyan Li,Hao Cao,Chuanxue Yang,Tianxiao Mei,Laihai Zhang,Yibing Wang,Wenwen Jia,Wen Sun,Yihui Hu,Zhongmin Liu
Cell therapy is a promising approach for myocardial infarction (MI) treatment. However, this strategy is often restricted by the harsh microenvironment of MI, such as excess ROS, high oxidative stress, inflammation, etc., and thus decreases the curative effect. Additionally, the distribution, migration, and homing of the transplanted stem cells is ambiguous, which also becomes a bottleneck for clinical translation. To address these challenges, herein, a versatile antioxidant nanozyme is designed by polymerically modifying dopamine (PDA) onto the surface of Mn 3 O 4 . The obtained nanozyme acts as an efficient SOD mimic, eliminating ROS, relieving oxidative stress, and reducing inflammation to improve the MI microenvironment. Simultaneously, Mn 3 O 4 @PDA serves as an excellent MRI contrast agent for tracking MSCs. Then, MSCs are engineered with Mn 3 O 4 @PDA nanozyme via endocytosis to form Mn 3 O 4 @PDA-MSCs (Abbr. E-MSCs), which possess superior viability, migration and homing ability compared to normal MSCs. Furthermore, E-MSCs exhibit superior anti-oxidant and anti-inflammatory activity, thereby enhancing the therapeutic efficacy of MSCs. Finally, the in vivo MRI tracking and synergistic therapy potential of E-MSCs is explored in MI model mice. Overall, this work provides a strategy to combine antioxidant activity and imaging properties of nanozymes to simultaneously facilitate imaging tracking of stem cells and improve MI treatment.
研究领域:
纳米技术
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干细胞治疗
·
心脏病学
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医学影像
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生物医学工程
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Qianyu Yang,Gang Wu,Yefeng Yang,Yang Zhou,Jiali Song,Huile Gao,Weiyuan Huang
Based on the properties of photodynamic therapy (PDT) and magnetic resonance imaging (MRI), combining them to construct multifunctional nanotheranostics can leverage strengths and avoid weaknesses for tumor diagnosis and treatment. However, certain problems remain unsolved, notably the short observation window caused by insufficient retention time. In this study, a GSH-responsive shape-transformable nanotheranostics Gd-Ce6-FFVLGGGC-SS-PEG are designed (abbreviated as GdCFS) by combining a single metal Gd with Ce6, and peptide (Phe-Phe-Val-Leu-Gly-Gly-Gly-Cys) disulfide-conjugated with polyethylene glycol (PEG) to perform dual-modal T 1 /T 2 MRI specifically at the tumor site. Due to its amphiphilic features, GdCFS can self-assemble to spherical nanoparticles, while transforming to nanofibers (NFs) in the presence of intracellular overexpressed GSH stimuli. After NFs formation, the hydrophobic core of GdCFS is exposed, resulting in T 1 positive contrast enhancement, whereas NFs can simultaneously achieve T 2 negative contrast enhancement. Furthermore, GSH depletion can cause imbalance in intracellular redox state, ultimately improving PDT efficacy. GdCFS benefits from the shape-transformation in terms of sufficient retention time, thus positively minimizing the toxicity risk. On the tumor model of nasopharyngeal carcinoma, in vivo and in vitro outcomes confirm that GdCFS can be a promising candidate for early diagnosis, real-time monitoring, and precise treatment of tumors with great biocompatibility.
研究领域:
医学
·
纳米医学
·
肿瘤学
·
影像学
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DOI
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 36
·8271-8281
·
IF 5.344
Daquan Wang,Ning Zhang,Xunan Jing,Yun Zhang,Yanzi Xu,Lingjie Meng
Multifunctional intelligent theranostics agents are promising for next-generation oncotherapy. We fabricated a tumor-microenvironment (TME)-responsive carbon nanotube (CNT)-based nanoplatform for T1 weighted magnetic resonance imaging (MRI)-guided synergistic photodynamic and photothermal therapy (PDT and PTT). CNTs convert near infrared (NIR) radiation into hyperthermia for PTT, and can effectively deliver their cargo into cells due to their unique 1D nanostructure. The CNT@MnO2-PEG@Ce6 nanomedicine was internalized into tumor cells, and rapidly released the photosensitizer (Ce6) in response to the low pH and high glutathione (GSH) levels characteristic of the TME. The degradation of the MnO2 layer under the same conditions released Mn2+ for T1-MRI. Furthermore, catalytic decomposition of the excess H2O2 into oxygen by MnO2 enhanced the efficacy of PDT, relieved hypoxia, and increased consumption of superfluous GSH to mitigate the effects of excessive reactive oxygen species (ROS) generation during PDT. MRI-guided PDT and PTT synergistically inhibited tumor cell growth in vitro, and ablated tumors in vivo. The side effects were negligible due to specific tumor cell targeting via surface modification with folic-PEG, and enhanced permeability and retention. Taken together, CNT@MnO2-PEG is a fully TME-responsive theranostics nanoplatform for targeted tumor ablation and real-time disease tracking.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2021
·
IF 7.446
Keyu Chen,Pan Li,Chunrong Zhu,Zhiyang Xia,Qian Xia,Lei Zhong,Bin Xiao,Tao Cheng,Changqiang Wu,Chengyi Shen,Xiaoming Zhang,Jiang Zhu
Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.
研究领域:
医学影像
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药物化学
·
放射学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Xu Kaiwei,Jin Lufei,Xu Liu,Zhu Yuchao,Hong Lu,Pan Chunshu,Li Yanying,Yao Junlie,Zou Ruifen,Tang Weiwei,Wang Jianhua,Wu Aiguo,Ren Wenzhi
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO2-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO2-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.
研究领域:
肿瘤学
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纳米技术
·
生物医学工程
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癌症治疗
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医学影像
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Yongqiang Li,Hui Dong,Quan Tao,Caichao Ye,Mengmeng Yu,Jipeng Li,Huifang Zhou,Siwei Yang,Guqiao Ding,Xiaoming Xie
The design of contrast agents (CAs) with high magnetic relaxivities is a key issue in the field of magnetic resonance imaging (MRI). The traditional strategy employed is aimed at optimizing the structural design of the magnetic atoms in the CA. However, it is difficult to obtain an agent with magnetic relaxivity over 100 mM −1 s −1 using this approach. In this work, we demonstrate that modulation of the localized superacid microenvironment of certain CAs (Gd 3+ loaded polyethylene glycol modified graphene oxide quantum dots or ‘GPG’ for short) can effectively enhance the longitudinal magnetic relaxivities ( r 1 ) by accelerating proton exchange. r 1 values of a series of GPGs are significantly increased by 20–30 folds compared to commercially available CAs over a wide range of static magnetic field strengths (e.g. 210.9 mM −1 s −1 vs . 12.3 mM −1 s −1 at 114 μT, 127.0 mM −1 s −1 vs . 4.9 mM −1 s −1 at 7.0 T). GPG aided MRI images is then acquired both in vitro and in vivo with low biotoxicities. Furthermore, folic-acid-modified GPG is demonstrated suitable for MRI-fluorescence dual-modal tumor targeting imaging in animals with more than 98.3% specific cellular uptake rate.
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 31
·6956-6963
·
IF 5.344
Peisen Zhang,Zihua Wang,Yiyang Wang,Yuqing Wang,Chunyan Liu,Kai Cao,Yijie Lu,Leila Behboodpour,Yi Hou,Mingyuan Gao
MRI contrast agents such as paramagnetic Gd(III)-chelates, can improve the ability of MRI in differentiating diseased and healthy tissues, and have been widely used in clinical diagnosis. However, the enhancement effect of small molecular MRI contrast agents is unsatisfied due to their relative high rotation rates. Furthermore, the small molecular contrast agents also suffer from the short blood half-life and nonspecific extracellular diffusion in tissues, which also restricts their applications. To address these issues, we developed a macromolecular MRI contrast agent based on a zwitterionic metal-chelating polymer. Poly(acrylic acid) (PAA) was chosen as the main chain, and diethylenetriamine pentaacetic acid (DTPA) as the metal-chelating group was coupled through the carboxyl groups of PAA using diethylenetriamine (DET) as a linker. The macromolecular MRI contrast agent constructed by chelating with Gd3+ (Gd-PAA) exhibited a much higher longitudinal relaxation rate (r1) than the clinical contrast agent Gd-DTPA. Importantly, due to the stealth ability of the zwitterionic structure, Gd-PAA can reside in the blood long enough without any microvascular leakage in the extracellular space of normal tissues, which allows it to be used for precise blood MR imaging, such as hepatorenal angiography, but also for tumor imaging because of the enhanced permeability and retention (EPR) effecta. Besides, the result of long-term toxicity tests highlights the safety feature of the current contrast agent. Hence, the current contrast agent overcomes the defect of traditional small molecular Gd(III)-based T1-weighted contrast agents and shows great prospects for future clinical applications.
研究领域:
医学影像学
·
生物材料学
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DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 32
·16738-16754
·
IF 6.895
Weidong Fei,Danfei Chen,Hongxia Tang,Chaoqun Li,Weizeng Zheng,Fengying Chen,Qianqian Song,Yunchun Zhao,Yu Zou,Caihong Zheng
Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese–oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.
研究领域:
纳米技术
·
癌症研究
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磁共振成像
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诊疗学
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DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 34
·19397-19407
·
IF 3.049
Jie Yin,Guangfu Yin,Ximing Pu,Zhongbing Huang,Dajin Yao
As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) are required to exhibit both low cytotoxicity and specific targetability besides superparamagnetism to achieve better imaging contrast at lower dose, and cladding with biocompatible polymers and modification with targeting ligands are considered to be the most effective strategies. In this study, novel dextran wrapped and peptide WSGPGVWGASVK (peptide-WSG) grafted USPIOs were meticulously prepared and systematically characterized. Firstly, dextran (Dex) cladded USPIOs (USPIOs@Dex) were synthesized with a well-designed co-precipitation procedure in which the biocompatible dextran played dual roles of grain inhibitor and cladding agent. After that, sodium citrate was applied to carboxylize the hydroxyls of the dextran molecules via an esterification reaction, and then tumor targeting peptide-WSG was grafted to the carboxyl groups by the EDC method. The XRD, TEM, and FTIR results showed that inverse spinel structure Fe3O4 crystallites were nucleated and grown in aqueous solution, and the catenulate dextran molecules gradually bound on their surface, meanwhile the growth of grains was inhibited. The size of original crystallite grains was about 7 nm, but the mean size of USPIOs@Dex aggregates was 165.20 nm. After surface modification by sodium citrate and peptide-WSG with ultrasonic agitation, the size of the USPIOs@Dex-WSG aggregates was smaller (66.06 nm) because the hydrophilicity was improved, so USPIOs@Dex-WSG could evade being eliminated by RES more easily, and prolong residence time in blood circulation. The VSM and T2-weighted MRI results showed that USPIOs@Dex-WSG were superparamagnetic with a saturation magnetization of 44.65 emu g−1, and with high transverse relaxivity as the R2 relaxivity coefficient value was 229.70 mM−1 s−1. The results of MTT assays and the Prussian blue staining in vitro revealed that USPIOs@Dex-WSG exhibited nontoxicity for normal cells such as L929 and HUVECs, and were specifically targeted to the SKOV-3 cells. Thus, the novel dextran wrapped and WSG-peptide grafted USPIOs have potential to be applied as tumor active targeting contrast agents for MRI.
研究领域:
生物医学工程
·
材料科学
·
医学影像学
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2021
·
IF 3.882
Mengjiao Yi,Lin Ma,Wenrong Zhao,Jie Zhao,Qi Fan,Jingcheng Hao
Cationic magnetic Gemini surfactants (mag-G-surfs), [C14H29(CH3)2N(CH2)2N(CH3)2C14H29]2+·2[XCl3Br]− (14-2-14·2X, X = Ce, Gd, or Ho), efficiently induce the aggregation of glutathione-protected Au nanoclusters (NCs) (GSH-Au NCs). These magnetic luminescent aggregates not only possess aggregation-induced emission (AIE) behavior but also display aggregation-induced magnetic enhancement. In particular, 14-2-14·2Ce and 14-2-14·2Gd have a better effect on boosting the luminescence intensity, quantum yield (QY), and luminescence lifetime (τ). The luminescent aggregates of GSH-Au NCs triggered by 14-2-14·2Gd or 14-2-14·2Ho exhibit more favorable paramagnetic behavior. Other Au NCs containing a Au(I)–thiolate complex shell also exhibit the obvious AIE phenomenon after introducing 14-2-14·2Gd, demonstrating the luminescence enhancement effect of mag-G-surfs. The luminescent aggregate 14-2-14·2Ce@GSH-Au NCs can serve as a “light up” fluorometric probe to detect cysteine selectively with the detection limit (DL) of 36 μM, and the magnetic luminescent aggregate 14-2-14·2Gd@GSH-Au NCs has the potential to be a novel contrast agent in T1-weighted magnetic resonance (MR) imaging due to its satisfactory contrasting ability.
研究领域:
分析化学
·
材料科学
·
医学影像学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Jingya Qin,Qiuming Liu,Junxue Zhang,Jing Chen,Shuai Chen,Yao Zhao,Jianzhong Du
It is an important challenge to in situ grow ultrafine super-paramagnetic iron oxide nanoparticles (SPIONs) in drug carriers such as polymer vesicles (also called polymersomes) while keeping their biodegradability for enhanced T2-weighted magnetic resonance imaging (MRI) and drug delivery. Herein, we present a new strategy by rationally separating the corona and membrane functions of polymer vesicles to solve the above problem. We designed a poly(ethylene oxide)-block-poly(ε-caprolactone)-block-poly(acrylic acid) (PEO43-b-PCL98-b-PAA25) triblock copolymer and self-assembled it into polymer vesicle. The PAA chains in the vesicle coronas are responsible for the in situ nanoprecipitation of ultrafine SPIONs, while the vesicle membrane composed of PCL is biodegradable. The SPIONs-decorated vesicle is water-dispersible, biocompatible, and slightly cytotoxic to normal human cells. Dynamic light scattering, transmission electron microscopy, energy disperse spectroscopy, and vibrating sample magnetometer revealed the formation of ultrafine super-paramagnetic Fe3O4 nanoparticles (1.9 ± 0.3 nm) in the coronas of polymer vesicles. Furthermore, the CCK-8 assay revealed low cytotoxicity of vesicles against normal L02 liver cells without and with Fe3O4 nanoparticles. The in vitro and in vivo MRI experiments confirmed the enhanced T2-weighted MRI sensitivity and excellent metastasis in mice. The loading and release experiments of an anticancer drug, doxorubicin hydrochloride (DOX·HCl), indicated that the Fe3O4-decorated magnetic vesicles have potential applications as a nanocarrier for anticancer drug delivery. Moreover, the polymer vesicle is degradable in the presence of enzyme such as Pseudomonas lipases, and the ultrafine Fe3O4 nanoparticles in the vesicle coronas are confirmed to be degradable under weakly acidic conditions. Overall, this decoration-in-vesicle-coronas strategy provides us with a new insight for preparing water-dispersible ultrafine super-paramagnetic Fe3O4 nanoparticles with promising theranostic applications in biomedicine.
研究领域:
生物医学工程
·
材料科学
·
医学影像学
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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）