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Doping engineering of iron oxide nanoparticles towards high performance and biocompatible T_(1)-weighted MRI contrast agents

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Rare Metals 2024年第1期43卷 298-308页

作者： Xue Xu Ping-Li Dong Yu-Yun Chai Run Yang Zhen-Hui Ma Chi-Chong Lu Department of Chemistry College of Chemistry and Materials EngineeringBeijing Technology and Business UniversityBeijing 100048China Department of Physics Beijing Technology and Business UniversityBeijing 100048China

Extremely small-sized iron oxide nanoparticles(IONPs) are of great interest in magnetic resonance imaging(MRI) due to their biosafety as an alternative to clinical gadolinium(Ⅲ) complexes-based contrast agents.Especially when the particle size is less than 10 nm,it has strong diffusion ability and deep penetration distance in tumor tissue.Substitution doping can significantly enhance the T_(1)contrast effect of nanoparticles by regulating the surface exposed atoms.However,the nucleation and growth processes of multi-component synthesis systems are complex and difficult to be accurately controlled,leading to great challenges in the synthesis of ultra-small-sized nanoparticles with different components and sizes.Here,extremely smallsized superparamagnetic gadolinium-doped iron oxide nanoparticles(GdIONPs,Gd_(x)Fe_(3-x)O_(4) NPs) with adjustable doping amount and controllable size in the range of 3.5-7.5 nm were synthesized by thermal decomposition.Then,as-synthesized GdIONPs were surface modified with a highly water-soluble and biocompatible carboxyl-polyethylene glycol-phosphoric acid ligand with high binding affinity.Gd_(0.65)Fe_(2.35)O_(4) NPs exhibited very high r_(1) relaxivity of 10.6 mmol^(-1)·L·s^(-1) in terms of all metal concentrations and 49.0 mmol^(-1)·L·s^(-1) in terms of gadolinium alone,respectively,3 and 14 times higher than clinical T_(1) contrast agents(Gd-DTPA).GdIONPs can continuously obtain high resolution images of blood vessels,and can be used as an efficient and multifunctional contrast agent for MR T_(1)imaging.This stable and efficient doping strategy provides an easy and effective method to individually optimize the magnetic properties of complex oxides and their relaxation effects for a variety of biomedical applications.

关键词： iron oxide nanoparticles Small size Magnetic resonance imaging Substitutional doping Gd dopant

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iron oxide nanoparticles:A promising approach for diagnosis and treatment of cardiovascular diseases

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Nano Research 2023年第11期16卷 12453-12470页

作者： Xue Bao Yu Mao Guangxiang Si Lina Kang Biao Xu Ning Gu Cardiovascular Disease Research Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolMedical SchoolNanjing UniversityNanjing 210093China State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Sciences and Medical EngineeringSoutheast UniversityNanjing 210096China

Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden.iron oxide nanoparticles(IONPs),with their unique magnetism and bioproperties,have shown great potential in this regard.In this review,we will begin with a brief overview of the synthesis and properties of IONPs.We will then focus on the latest applications of IONPs in CVDs,including diagnosis and treatment.The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field,and will be addressed in a separate section.The translational potential and challenges of IONPs will also be discussed.In conclusion,ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively,and offer more personalized and efficient options for the diagnosis and treatment of CVDs.

关键词： atherosclerosis cardiovascular disease diagnosis iron oxide nanoparticles theranostic treatment

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Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging

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Bioactive Materials 2022年第6期7卷 214-245页

作者： Zhenghuan Zhao Muyao Li Jie Zeng Linlin Huo Kun Liu Ruixue Wei Kaiyuan Ni Jinhao Gao College of Basic Medical Sciences Chongqing Medical UniversityChongqing400016China State Key Laboratory of Physical Chemistry of Solid Surfaces The Key Laboratory for Chemical Biology of Fujian ProvinceAnd Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen UniversityXiamenFujian361005China Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Koch Institute for Integrative Cancer Research Massachusetts Institute of TechnologyCambridgeMA02142United States

iron oxide nanoparticle(IONP)with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging(MRI)contrast agent(CA)for long time.However,a review which comprehensively summarizes the recent development of IONP as traditional T_(2) CA and its new application for different modality of MRI,such as T_(1) imaging,simultaneous T_(2)/T_(1) or MRI/other imaging modality,and as environment responsive CA is rare.This review starts with an investigation of direction on the development of high-performance MRI CA in both T_(2) and T_(1) modal based on quantum mechanical outer sphere and Solomon-Bloembergen-Morgan(SBM)theory.Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters,including magnetization,size,effective radius,inhomogeneity of surrounding generated magnetic field,crystal phase,coordination number of water,electronic relaxation time,and surface modification are summarized.Besides the strategies to improve r2 or r1 values,strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects,those are introducing second imaging modality to increase the imaging accuracy,endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue,and optimizing the interface structure to improve the accumulation amount of IONP in lesion.This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs.It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.

关键词： iron oxide nanoparticles Improved relaxation Dual-modal contrast imaging Environment responsive imaging Strcture engineering

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Spy chemistry enables stable protein immobilization on iron oxide nanoparticles with enhanced magnetic properties

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Journal of Materials Science & Technology 2023年第30期161卷 161-169页

作者： Chu Shi Jingyi Sheng Guangxiang Si Yan Li Yan Shen Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210009China School of Biomedical Engineering and Informatics Nanjing Medical UniversityNanjing 211166China Medical School Nanjing UniversityNanjing 210093China

iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.

关键词： iron oxide nanoparticles Spy chemistry Protein immobilization Magnetic resonance imaging Cell labeling

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Highly Efficient Labeling of Human Lung Cancer Cells Using Cationic Poly-L-lysine-Assisted Magnetic iron oxide nanoparticles

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Nano-Micro Letters 2015年第4期7卷 374-384页

作者： Xueqin Wang Huiru Zhang Hongjuan Jing Liuqing Cui College of Bioengineering Henan University of Technology

Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.

关键词： Magnetic labeling iron oxide nanoparticles Poly-L-lysine Human A549 lung cancer cells Cancer treatment

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Inhibition of furin by bone targeting superparamagnetic iron oxide nanoparticles alleviated breast cancer bone metastasis

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Bioactive Materials 2021年第3期6卷 712-720页

作者： Yichuan Pang Li Su Yao Fu Fan Jia Chenxi Zhang Xiankun Cao Wenxin He Xueqian Kong Jiake Xu Jie Zhao An Qin Shanghai Key Laboratory of Orthopedic Implants Department of OrthopaedicsShanghai Ninth People's HospitalShanghai Jiaotong University School of MedicineShanghai200011China Department of Nuclear Medicine Shanghai Tenth People's HospitalTongji University School of MedicineShanghai200072China Hongqiao International Institute of Medicine Shanghai Jiaotong University School of Medicine201103China Center for Chemistry of High-Performance&Novel Materials Department of ChemistryZhejiang UniversityHangzhou310027China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China School of Biomedical Sciences The University of Western AustraliaPerthWestern Australia6009Australia

Breast cancer bone metastasis poses significant challenge for therapeutic strategies.Inside the metastatic environment,osteoclasts and tumor cells interact synergistically to promote cancer progression.In this study,the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function.Importantly,the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide(SPIO)nanoparticles.Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion,leading to alleviated osteolysis.Therefore,the bone targeting&furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.

关键词： Breast cancer metastasis Osteoclast Furin Bone targeting iron oxide nanoparticles

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Structural effects on the magnetic hyperthermia properties of iron oxide nanoparticles

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Progress in Natural Science:Materials International 2016年第5期26卷 440-448页

作者： Eric C.Abenojar Sameera Wickramasinghe Jesbaniris Bas-Concepcion Anna Cristina S.Samia Department of Chemistry Case Western Reserve University Chemistry Department University of Puerto Rico Rio Piedras Campus

Magnetic iron oxide nanoparticles(IONPs) are heavily explored as diagnostic and therapeutic agents due to their low cost, tunable properties, and biocompatibility. In particular, upon excitation with an alternating current(AC) magnetic field, the NPs generate localized heat that can be exploited for therapeutic hyperthermia treatment of diseased cells or pathogenic microbes. In this review, we focus on how structural changes and inter-particle interactions affect the heating efficiency of iron oxide-based magnetic NPs. Moreover, we present an overview of the different approaches to evaluate the heating performance of IONPs and introduce a new theranostic modality based on magnetic imaging guided–hyperthermia.

关键词： iron oxide nanoparticles Magnetic hyperthermia Magneto-structural effects Magnetic dipolar interactions Magnetic imaging guided–hyperthermia

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M2 macrophage-targeted iron oxide nanoparticles for magnetic resonance image-guided magnetic hyperthermia therapy

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Journal of Materials Science & Technology 2021年第22期81卷 77-87页

作者： Wenshen Wang Fenfen Li Shibo Li Yi Hu Mengran Xu Yuanyuan Zhang Muhammad Imran Khan Shaozhen Wang Min Wu Weiping Ding Bensheng Qiu National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering University of Science and Technology of ChinaHefei230027China The First Affiliated Hospital of Anhui Medical University Hefei230022China

Tumor-associated macrophages(TAMs)play an important role in tumor development and progression.In particular,M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors.Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment.iron oxide nanoparticles based magnetic hyperthermia therapy(MHT)is a classical approach to destroy tumor tissue with deep penetration depth.In this study,we developed a typical M2 macrophage-targeted peptide(M2pep)functionalized superparamagnetic iron oxide nanoparticle(SPIO)for magnetic resonance imaging(MRI)-guided MHT in an orthotopic breast cancer mouse model.The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability,high transverse relaxivity(149 mM^(-1) s^(-1))and satisfactory magnetic hyperthermia performance in vitro.In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT.The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor.In addition,the SPIO-M2pep based MHT can remodel the tumor immune microenvironment(TIME).The multifunctional SPIO-M2pep with M2 macrophage-targeting ability,high magnetic hyperthermia efficiency,MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

关键词： M2 macrophages-targeted peptide iron oxide nanoparticles Magnetic resonance imaging Magnetic hyperthermia therapy Tumor immune microenvironment

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Effects of surface modifications on the physicochemical properties of iron oxide nanoparticles and their performance as anticancer drug carriers

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Chinese Chemical Letters 2018年第12期29卷 1829-1833页

作者： Lingling Guo Hong Chen Nongyue He Yan Deng State Key Laboratory of Bioelectronics National Demonstration Center for Experimental Biomedical Engineering EducationSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province Hunan Key Laboratory of Biomedical Nanomaterials and DevicesHunan University of TechnologyZhuzhou 412007China School of Materials Science and Energy Engineering Foshan UniversityFoshan 528000China

The feature of the surface coating can affect important properties of iron oxide nanoparticles(IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is still needed to fully exploit the potential of IONPs for their theranostic applications. In this work, we prepared IONPs which surface were modified with citric acid(CA), chitosan(CS) and folic acid conjugated chitosan(FA-g-CS). respectively. Their physicochemical properties were investigated using FT-IR, TEM,powder XRD, VSM, TGA, DLS and zeta potential. We found that CA-IONP dispersion was composed of monocrystalline particles while CS-IONP and FA-g-CS-IONP were composed of polycrystalline aggregates. All IONPs retained the crystalline structure of magnetite and exhibited the superparamagnetic behavior. Their saturation magnetization decreased with the increase in the amount of their organic coatings. Their drug loading capacities, drug release patterns and in vitro anticancer efficiencies were studied by using doxorubicin(DOX) as a model drug. DOX@CS-IONP and DOX@FA-g-CSIONP exhibited lower drug loading while showing higher water dispersity when compared with DOX@CA-IONP. All IONPs were surface charged and they tended to agglomerate in medium with high pH value and ionic strength. In the presence of chitosan or FA-g-CS coatings, their DOX release rate was slowed down compared with that of DOX@CA-IONP. Unloaded IONPs exhibited nearly no cytotoxicity on both cancer cells and normal cells in the presence of chitosan and FA-g-CS when compared with CA-IONP which presented high cytotoxicity. However, DOX@FA-g-CS-IONP showed significantly cytotoxicity on folate receptors(FRs) positive breast cancer cells while exhibiting nearly no cytotoxicity on FRs negative normal cells. Results presented in this study were valuable to the design and fabrication of IONPs-based system for better theranostic applications.

关键词： iron oxide nanoparticles Surface modification Physicochemical property Drug delivery Chitosan Folic acid

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Balanites aegyptiaca Oil Synthesized iron oxide nanoparticles: Characterization and Antibacterial Activity

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Journal of Biomaterials and Nanobiotechnology 2016年第3期7卷 154-165页

作者： Hind Baballa Gasmalla Ahmed Mahmoud Idris Mahgoub Ibrahim Shinger Dongdong Qin Duoliang Shan Xiaoquan Lu Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province College of Chemistry & Chemical Engineering Northwest Normal University Lanzhou China Forest Products and Industries Department Faculty of Forestry University of Khartoum Khartoum Sudan Chemistry Department Faculty of Science International University of Africa Khartoum Sudan

Antibacterial activity of iron oxide nanoparticles, an employing B. aegyptiaca oil (L.) Del., was used as natural stabilizer by modifying a co-precipitation method. In this work, we chose B. aegyptiaca oil as the new surfactant coating agent, and synthesized B. aegyptiaca oil coating with iron oxide nanoparticles which were characterized with a variety of methods, including Gas Chromatography (GC) to determine the fatty acids composition of the seeds oil, Fourier Transform-Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM) equipped with Energy Dispersive Spectroscopy (EDS), X-ray Powder Diffractometer (XRD) and Vibrating Sample Magnetometer (VSM). In antibacterial studies, disk diffusion susceptibility test was used to measure efficacy of iron oxide nanoparticles against Gram-positive bacteria Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis) and Gram-negative bacteria Escherichia coli (E. coli) in terms of zone inhibition. The B. aegyptiaca coated on the surface of iron oxide nanoparticles;its particle size was found to be nanoscale below 50 nm, and the magnetization (δs) was 16.975 emu g-1. Antibacterial activity was measured. Efficacy of iron oxide nanoparticles against bacterial strains was found in Escherichia coli (E. coli). All these findings suggest that the nanoparticles synthesized from B. aegyptiaca oil may be a promising reagent for a wide variety of applications in biological fields as well as in nanomedicine.

关键词： iron oxide nanoparticles Balanites aegpyptiaca Oil Antibacterial Activity

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