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Scalable synthesis of lipid nanoparticles for nucleic acid drug delivery using an isometric channel-size enlarging strategy

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Nano Research 2024年第4期17卷 2899-2907页

作者： Zesen Ma Haiyang Tong Sijin Lin Li Zhou Demeng Sun Baoqing Li Changlin Tian Jiaru Chu Department of Precision Machinery and Precision Instrumentation University of Science and Technology of ChinaHefei 230027China key laboratory of Precision Scientific Instrumentation of anhui higher Education Institutes University of Science and Technology of ChinaHefei 230027China Science Island Branch Graduate SchoolUniversity of Science and Technology of ChinaHefei 230026China anhui provincial key laboratory of high field magnetic resonance imaging High Magnetic Field LaboratoryHefei Institute of Physical ScienceChinese Academy of SciencesHefei 230031China anhui provincial Engineering laboratory of Peptide Drugs University of Science and Technology of ChinaHefei 230027China School of Biomedical Engineering Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaSuzhou 215127China

Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable synthesis techniques that can consistently produce formulations from early development to clinical application.In this work,we proposed a method to achieve scalable synthesis of LNPs by scaling inertial microfluidic mixers isometrically in three dimensions.Moreover,a theoretical predictive method,which controls the mixing time to be equal across different chips,is developed to ensure consistent particle size and size distribution of the synthesized LNPs.LNPs loaded with small interfering RNA(siRNA)were synthesized at different flow rates,exhibiting consistent physical properties,including particle size,size distribution and encapsulation efficiency.This work provides a practical approach for scalable synthesis of LNPs consistently,offering the potential to accelerate the transition of nucleic acid drug development into clinical application.

关键词： lipid nanoparticles nucleic acid delivery microfluidics scalable synthesis consistent particle size

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Structure and ion transport properties of organic ionic compounds revealed by NMR

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magnetic resonance Letters 2024年第2期4卷 2-12页

作者： Haijin Zhu Guangdong provincial key laboratory of Materials and Technologies for Energy Conversion Guangdong Technion-Israel Institute of TechnologyShantou515063China

Organic ionic plastic crystals(OIPCs)are emerging as an important material family for solid-state electrolytes and many other applications.They have significant advantages over conventional electrolyte materials,such as high ionic conductivity,non-flammability,and plasticity.Various nuclear magnetic resonance(NMR)spectroscopy techniques including solid-state NMR,pulsed-field gradient(PFG)NMR,and magnetic resonance imaging(MRI)etc.,provide us a versatile toolkit to understand the fundamental level structures,molecular dynamics,and ionic interactions in these materials.This article reviews the commonly used NMR methods including solid-and solution-state NMR,PFG-NMR,dynamic nuclear polarization(DNP)and the application of these methods in revealing the microscopic level structures and ion-transport mechanisms in OIPC materials.

关键词： NMR Electrolyte Organic ionic plastic crystals Defects Diffusion Microstructure

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Rheo-NMR: A versatile hyphenated technique for capturing molecular dynamics and structure under flow

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magnetic resonance Letters 2024年第1期4卷 50-60页

作者： Yuqi Xiong Zishuo Wu Lei Wu Chengyan Li Wei Chen National Synchrotron Radiation laboratory Anhui Provincial Engineering Laboratory of Advanced Functional Polymer FilmCAS Key Laboratory of Soft Matter ChemistryUniversity of Science and Technology of ChinaHefei230026China Department of Accelerator Science and Engineering Physics School of Nuclear Science and TechnologyUniversity of Science and Technology of ChinaHefei230026China

The general development of Rheo-NMR during the last four decades as well as selective hyphenated apparatuses is presented.Based on different magnet types,the current review is divided into two categories,namely low-field and high-field NMR,while the timedomain NMR is normally applied in the former case and the frequency-domain NMR is adopted in the latter one.Depending on different rheometer cells,it can be further divided into tensile and shear mode Rheo-NMR.The combination of various rheometer cells and NMR facility guarantees our acquisition of molecular level structure and dynamics information under flow conditions,which is crucial for our understanding of the molecular origin of complex fluids.A personal perspective is also presented at last to highlight possible development in this direction.

关键词： Rheo-NMR Polymer deformation mechanism Polymer rheology Viscoelastic property

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A case report of bilateral lateral ventricle calcified pseudoneoplasm of the neuraxins

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Chinese Neurosurgical Journal 2024年第1期10卷 67-72页

作者： Xiaolong Qiao Yinan Chen Ying Ji Chaoshi Niu Chuandong Cheng anhui University of Science and Technology HuainanAnhui 232001People’s Republic of China Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China1st Tianehu RoadHefeiAnhui 230031People’s Republic of China

Background Calcifying pseudoneoplasm of the neuraxis(CAPNON)is indeed a rare central nervous system lesion that can occur in central nervous system(CNS).Due to its infrequency and limited literature reports,it is challenging to diagnose and manage CAPNON.Case presentation In this intriguing study,we embarked on a quest to uncover the story of a 16-year-old girl who experienced bothersome headaches.Through advanced imaging techniques like computed tomography(CT)and magnetic resonance imaging(MRI),we glimpsed a delicate calcified growth within the lateral ventricles’posterior horn.Motivated by our unwavering commitment to solving mysteries,we embarked on a surgical journey that not only freed the young patient from her ailment but also shed light on the true nature of her puzzling adversary—a remarkable CAPNON.Conclusions For patients with CAPNON who have multiple or non-respectable lesions,the primary goal is to alleviate symptoms.After alleviating the symptoms with partial resection,close monitoring of any residual lesions is essential.If there is no evidence for disease progression,a strategy of continued close observation is appropriate.

关键词： CAPNON imaging Pathology Operation

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Overview and progress of X-nuclei magnetic resonance imaging in biomedical studies

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magnetic resonance Letters 2023年第4期3卷 327-343页

作者： Gengxin Wang Hongyi Yang Juan Li Jie Wen Kai Zhong Changlin Tian Institutes of Physical Science and Information Technology Anhui UniversityHefei230601China anhui provincial key laboratory of high field magnetic resonance imaging High Magnetic Field LaboratoryHefei Institute of Physical ScienceChinese Academy of SciencesHefei230031China School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230026China The First Affiliation Hospital Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230001China Division of Medicine Peking UniversityBeijing100101China

Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.

关键词： magnetic resonance imaging X-nuclei Biomedical ^(13)C ^(17)O ^(19)F ^(23)Na ^(31)P

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Effects of gradient high-field static magnetic fields on diabetic mice

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Zoological Research 2023年第2期44卷 249-258页

作者： Biao Yu Chao Song Chuan-Lin Feng Jing Zhang Ying Wang Yi-Ming Zhu Lei Zhang Xin-Miao Ji Xiao-Fei Tian Guo-Feng Cheng Wei-Li Chen Vitalii Zablotskii Hua Wang Xin Zhang high magnetic field laboratory CAS Key Laboratory of High Magnetic Field and Ion Beam Physical BiologyHefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui 230031China Science Island Branch of Graduate School University of Science and Technology of ChinaHefeiAnhui 230026China Institutes of Physical Science and Information Technology Anhui UniversityHefeiAnhui230601China Institute of Physics of the Czech Academy of Sciences Prague18221Czech Republic Department of Oncology First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China International Magnetobiology Frontier Research Center Science IslandHefeiAnhui 230031China

Although 9.4 T magnetic resonance imaging(MRI) has been tested in healthy volunteers,its safety in diabetic patients is unclear.Furthermore,the effects of high static magnetic fields(SMFs),especially gradient vs.uniform fields,have not been investigated in diabetics.Here,we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients(>10 T/m vs.0-10 T/m)on type 1 diabetic(T1D) and type 2 diabetic(T2D) mice.We found that 14 h of prolonged treatment of gradient(as high as 55.5 T/m) high SMFs(1.0-8.6 T) had negative effects on T1D and T2D mice,including spleen,hepatic,and renal tissue impairment and elevated glycosylated serum protein,blood glucose,inflammation,and anxiety,while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects.In regular T1D mice(blood glucose>16.7 mmol/L),the>10 T/m gradient high SMFs increased malondialdehyde(P10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate.In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation.Therefore,this study showed that prolonged exposure to high-field(1.0-8.6 T)>10 T/m gradient SMFs(35-1 380 times higher than that of current clinical MRI)can have negative effects on diabetic mice,especially mice with severe T1D,whereas 9.4 T high SMFs at 0-10T/m did not produce the same effects,providing important information for the future development and clinical application of SMFs,especially high-field MRI.

关键词： Type 2 diabetes Type 1 diabetes magnetic resonance imaging(MRI) Gradient static magnetic field Quasi-uniform static magnetic field

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Terahertz magnetic resonance in MnCr_(2)O_(4)under high magnetic field

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Chinese Physics B 2022年第10期31卷 534-538页

作者：张朋贺凯博王铮张仕乐戴建明苏付海 Department of Physics Laboratory of Functional Materials and Device for InformaticsFuyang Normal UniversityFuyang 236037China anhui provincial key laboratory of Condensed Matter Physics at Extreme Conditions High Magnetic Field LaboratoryHefei Institute of Physical Science(HFIPS)Chinese Academy of SciencesHefei 230031China key laboratory of Materials Physics Institute of Solid State PhysicsHFIPSChinese Academy of SciencesHefei 230031China

Terahertz(THz)time-domain spectroscopy(THz-TDS)of polycrystalline MnCr_(2)O_(4)was performed at<9 T and low temperatures.A resonance absorption in the sub-THz range with linear blueshifts was observed as the magnetic ... 详细信息

Terahertz(THz)time-domain spectroscopy(THz-TDS)of polycrystalline MnCr_(2)O_(4)was performed atresonance absorption in the sub-THz range with linear blueshifts was observed as the magnetic field was increased from 4 T to 9 T.These magnetism-driven absorptions originated from a ferromagnetic resonance,which agrees with low-field electron spin resonance measurements and ferromagnetic resonance theory.The low-temperature g-factors of MnCr_(2)O_(4)were also obtained using THz-TDS.This work provides new insights into the spin dynamics of chromite spinel compounds in the THz region.

关键词： chromium spinel terahertz time-domain spectroscopy ferromagnetic resonance

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Temperature-and field angular-dependent helical spin period characterized by magnetic dynamics in a chiral helimagnet MnNb_(3)S_(6)

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Science China(Physics,Mechanics & Astronomy) 2023年第1期66卷 171-177页

作者： Liyuan Li Haotian Li Kaiyuan Zhou Yaoyu Gu Qingwei Fu Lina Chen Lei Zhang Ronghua Liu National laboratory of Solid State Microstructures School of Physics and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China New Energy Technology Engineering laboratory of Jiangsu Province&School of Science Nanjing University of Posts and TelecommunicationsNanjing 210023China anhui key laboratory of Condensed Matter Physics at Extreme Conditions High Magnetic Field LaboratoryHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China

The chiral magnets with topological spin textures provide a rare platform to explore topology and magnetism for potential application implementation.Here,we study the magnetic dynamics of several spin configurations on the monoaxial chiral magnetic crystal MnNb_(3)S_(6)via broadband ferromagnetic resonance(FMR)technique at cryogenic temperature.In the high-field forced ferromagnetic state(FFM)regime,the obtained frequency f vs.resonance field H_(res) dispersion curve follows the wellknown Kittel formula for a single FFM,while in the low-field chiral magnetic soliton lattice(CSL)regime,the dependence of H_(res) on magnetic field angle can be well-described by our modified Kittel formula including the mixture of a helical spin segment and the FFM phase.Furthermore,compared with the sophisticated Lorentz micrograph technique,the observed magnetic dynamics corresponding to different spin configurations allow us to obtain temperature-and field-dependent proportion of helical spin texture and helical spin period ratio L(H)/L(0)via our modified Kittel formula.Our results demonstrated that fieldand temperature-dependent nontrivial magnetic structures and corresponding distinct spin dynamics in chiral magnets can be an alternative and efficient approach to uncovering and controlling nontrivial topological magnetic dynamics.

关键词： chiral helimagnets magnetic solitons ferromagnetic resonance phase diagram

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Flexible reduced field of view magnetic resonance imaging based on single-shot spatiotemporally encoded technique

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Chinese Physics B 2015年第10期24卷 629-637页

作者：李敬蔡聪波陈林陈颖屈小波蔡淑惠 Department of Electronics Science Fujian Provincial Key Laboratory of Plasma and Magnetic ResonanceXiamen University Department of Communication Engineering Xiamen University Center for Brain imaging Science and Technology Zhejiang University

In many ultrafast imaging applications, the reduced field-of-view（r FOV） technique is often used to enhance the spatial resolution and field inhomogeneity immunity of the images. The stationary-phase characteristic of the spatiotemporallyencoded（SPEN） method offers an inherent applicability to r FOV imaging. In this study, a flexible r FOV imaging method is presented and the superiority of the SPEN approach in r FOV imaging is demonstrated. The proposed method is validated with phantom and in vivo rat experiments, including cardiac imaging and contrast-enhanced perfusion imaging. For comparison, the echo planar imaging（EPI） experiments with orthogonal RF excitation are also performed. The results show that the signal-to-noise ratios of the images acquired by the proposed method can be higher than those obtained with the r FOV EPI. Moreover, the proposed method shows better performance in the cardiac imaging and perfusion imaging of rat kidney, and it can scan one or more regions of interest（ROIs） with high spatial resolution in a single shot. It might be a favorable solution to ultrafast imaging applications in cases with severe susceptibility heterogeneities, such as cardiac imaging and perfusion imaging. Furthermore, it might be promising in applications with separate ROIs, such as mammary and limb imaging.

关键词： magnetic resonance imaging spatiotemporal encoding single shot reduced field-of-view

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Effects of 3.7 T-24.5 T high magnetic fields on tumor-bearing mice

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Chinese Physics B 2018年第11期27卷 649-658页

作者：田小飞王泽张磊郗传英皮雳齐紫平陆轻铀张欣 high magnetic field laboratory Key Laboratory of High Magnetic Field and Ion Beam Physical Biology Hefci Institutes of Physical Science Chinese Academy of Sciences Hefei 230031 China Institute of Physical Science and Information Technology Anhui University Hefei 230601 China Hefei National laboratory for Physical Sciences at Microscale University of Science and Technology of China Hefei 230026 China anhui Province key laboratory of Condensed Matter Physics at Extreme Conditions Hefei 230031 China

Since high magnetic field（MF） intensity can improve the image quality and reduce magnetic resonance imaging（MRI） acquisition time, the field intensity of MRIs has continued to increase over the past few decades. Although MRIs in most current hospitals are 0.5 T–3 T, there are preclinical studies have been carried out using 9.4 T MRI, and engineers are also putting efforts on building MRIs with even higher MFs. However, the accompanied safety issue of high-field MRIs is an emergent question to address before their clinical applications. In the meantime, the static magnetic field（SMF） has been shown to inhibit tumor growth in previous studies. Here, we investigated both the safety issue and the anti-tumor potentials of 3.7 T–24.5 T SMFs on GIST-T1 gastrointestinal stromal tumor-bearing nude mice. We followed up the mice three weeks after their exposure to high SMF and found that none of the mice died or had severe organ damage, except for slightly decreased food intake, weight gain, and liver function. Moreover, the tumor growth was inhibited by 3.7 T–24.5 T SMFs（up to ～54%）. It is interesting that the effects are more dependent on MF gradient than intensities, and for the same gradient and intensity, mice responded differently to hypogravity and hypergravity conditions. Therefore, our study not only demonstrated the safeness of high SMFs up to 24.5 T on mice but also revealed their anti-tumor potentials in the future.

关键词： static magnetic field （SMF） high magnetic field （MF） tumor magnetic field gradient

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