Table of Content

10 December 2022, Volume 43 Issue 12

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Contents

Cover and Content of Chemical Journal of Chinese Universities Vol.43 No.12(2022)

2022, 43(12):  1-6. 

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Volume Contents of Chemical Journal of Chinese Universities to Vol.43(2022)

2022, 43(12):  1-10. 

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Review

Research Progress in Bioimaging and Theranostics of Thioxanthene-hemicyanine Dyes

YAO Shankun, DING Weizhong, WU Yanping, CHEN Yuncong, GUO Zijian

2022, 43(12):  20220568.  doi:10.7503/cjcu20220568

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Thioxanthene-hemicyanine is a fluorescent dye in which a nitrogen heterocyclic cation moiety and a terminal amino， hydroxyl or alkoxy amino group are linked by π-conjugated bridge. Thioxanthene-hemicyanine has outstanding photophysical properties and great biocompatibility， and its unique near-infrared emission and photosensitive features enable it to play a crucial role in the study of fluorescence detection and tumor therapy. This article reviews the research and application of thioxanthene-hemicyanine-based fluorescent probes and photosensitive molecules in the recognition of various biomarkers and phototherapy of diseases， respectively.



Applications of Metal-organic Frameworks in Cancer Theranostics

DONG Mingjie, WANG Xuan, DONG Haifeng, ZHANG Xueji

2022, 43(12):  20220575.  doi:10.7503/cjcu20220575

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The rapid development of imaging technologies allows scientists and clinicians to understand the pathogenesis and pathological processes of cancer accurately and to personalize treatment strategies based on a patient’s condition. Cancer theranostic platforms combining various imaging and therapeutic agents into one entity for the diagnosis and treatment of cancer simultaneously have attracted great attention and been widely studied. Metal-organic frameworks（MOFs） are an interesting and unique porous organic-inorganic hybrid materials constructed by the self-assembly of organic linkers and metal ions/ion clusters. It has demonstrated great potential to be a platform for carrying cancer theranostic agents due to its unique characteristics， such as easy post-modification， adjustable porosity， tunable functionality， and designable topology. In this review， we focused on the strategies of incorporating theranostic agents into MOFs carriers and summarized the developments of MOFs as cancer theranostic platforms for diagnosis and treatment of cancer guided by various imaging technologies， including magnetic resonance imaging， X-ray computed tomography imaging， positron emission tomography imaging， optical imaging， and photoacoustic imaging. Moreover， the current challenges and perspectives of MOFs for cancer theranostics and their clinical translation were also addressed.



High-resolution in vivo Imaging， Diagnosis and Treatment Applications of Rare-earth-based Nanomaterials

ZHANG Qian, LIU Yawei, WANG Fan, LIU Kai, ZHANG Hongjie

2022, 43(12):  20220552.  doi:10.7503/cjcu20220552

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Fluorescence imaging with the advantages of high spatiotemporal resolution， fast feedback， non-invasiveness， and no ionizing radiation is an important bioimaging technology. Compared with the traditionally used visible and first near-infrared（NIR-I， 650—950 nm） windows， the second near-infrared（NIR-Ⅱ， 1000—1700 nm） window has lower scattering coefficients and biological autofluorescence， thus effectively improving the resolution， signal-to-noise ratio and penetration depth of bioimaging. Rare-earth-based nanoparticles（RENPs） possess large Stokes shift， high chemical stability， tunable fluorescence lifetimes， and narrow emission bands， making them important fluorescent imaging probes. In recent years， a series of RENPs with excellent NIR-Ⅱ fluorescence properties have been developed and applied to high-resolution in vivo fluorescence imaging， disease diagnosis and therapy. Herein， the recent research progress of RENPs in high-resolution in vivo fluorescence imaging and theranostics is comprehensively reviewed. Strategies for NIR-Ⅱ emission enhancement of RENPs， such as dopant regulation， matrix lattice selection， and composite sensitization， are summarized. And their functions of targeting accumulation， fluorescence sensing， disease diagnosis and treatment in multiple biomedical scenes are also introduced. Moreover， their applications in multiplexed imaging， multimodal imaging， and disease diagnosis and treatment are highlighted. Finally， a brief perspective for the future development and challenges of RENPs in biomedical applications is presented.



Advances in Biosensing and Imaging Based on the Integration of DNA and Upconversion Nanoparticles

ZHAO Hengzhi, YU Fangzhi, LI Xiangfei, LI Lele

2022, 43(12):  20220626.  doi:10.7503/cjcu20220626

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Deoxyribonucleic aicd（DNA） have been widely used in biosensing and imaging because of their molecular recognition properties and functions. Lanthanide-doped upconversion nanoparticles（UCNPs） have also attracted extensive attention in biomedical applications due to their unique optical properties. In particular， the elegant integration of UCNPs and DNA holds many unparalleled features and functions， advancing the development in the field of biological sensing and imaging. In this review， we summarized the advances in biosensing and imaging based on the integration of DNA and UCNPs. We mainly focused on the design principles of the developed methods， briefly introduced their applications， and discussed the current challenges and future perspectives in this field.



Applications of Self-assembled Peptide Probes in Magnetic Resonance Imaging

XU Haidong, WANG Rui, LIANG Gaolin

2022, 43(12):  20220440.  doi:10.7503/cjcu20220440

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Magnetic resonance imaging（MRI） is a powerful non-invasive biomedical diagnostic technique. Clinically， MRI requires contrast agents to improve imaging quality， thereby improving the diagnosis accuracy. Due to the superior signal amplification ability and biocompatibility， self-assembled peptide probes can be loaded with specific MRI molecules to achieve tumor targeting and enriching through the enzyme responsive self-assembly process. Thus， self-assembled peptide probes can enhance the MRI signal of tumor lesions， thereby further improving the accuracy and sensitivity of MRI. This review summarizes the recent progress of self-assembled peptide probes under different MRI modalities（ ¹H MRI， ¹⁹F MRI， dual nuclei MRI）， and highlights their potential for cancer diagnosis.



Chiral Nanomaterials： Bioimaging， Biosensing and Therapeutics

LU Meiru, ZHANG Hongyu, SHI Baimei, SUN Maozhong, XU Liguang, XU Chuanlai, KUANG Hua

2022, 43(12):  20220683.  doi:10.7503/cjcu20220683

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Chiral inorganic nanostructures not only display great flexibility in morphology and structure regulation and simplicity in surface functionalization， but also exhibit unique optical properties， showing great excellence in the application of biological field. This review comprehensively discusses the research progress of chiral nanotechnology in the biomedical field in recent years， focusing on the chiral metal- or semiconductor-based nanostructures in terms of the synthesis strategy， circular dichroism effect， mechanisms of optical chirality and their performances in biomedical applications such as bioimaging， biosensing， tumours and neurodegenerative diseases therapies. These researches of chiral nanomaterials enrich biochemical nanotechnology means， promote the progress of diagnosis and therapeutic techniques for major diseases such as cancer， give a boost to the chirality in life sciences， and encourage researchers to continue to explore and challenge this emerging field.



Research Progress of Organic Small Molecule Theranostic Probes Integrating Fluorescence Imaging and Chemotherapy

CHANG Tonghang, CHENG Zhen

2022, 43(12):  20220430.  doi:10.7503/cjcu20220430

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Combining diagnostic and therapeutic functions is an emerging strategy to treat diseases such as cancer. As a promising novel medical regimen， the integration of diagnosis and treatment has potential functions in rapidly obtaining in vivo information， improving biodistribution， reducing dosage， and reducing toxic and side effects. Especially， fluorescence imaging has been widely used in pre-clinical and clinical medical research. In recent years， near-infrared fluorescence imaging has progressed rapidly with improved penetration depth and imaging resolution for in vivo imaging. In this review， we summarized some recent researches on single-molecule based theranostic agents integrating fluorescence imaging and chemotherapy， and foresaw future research on theranostic probes.



Advances in Enzyme-load Nanocatalytic Systems for Disease Detection and Treatment

TANG Yujing, HU Min, WANG Xia, WANG Qigang

2022, 43(12):  20220640.  doi:10.7503/cjcu20220640

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Enzymes are highly specific and efficient catalysts that regulate cellular metabolic processes through complex and sequential biochemical reactions in the organelle. Inspired by cellular compartmentalization structures， the bionic design of nano-enzyme catalytic systems was studied to construct a structural domain-constrained enzyme catalytic microenvironments to effectively remove the substrate diffusion barriers and improve the catalytic activity of enzyme， which opened up new ideas for catalytic applications of enzymes. In addition， the small size， large specific surface area， and the electron paramagnetic resonance（EPR） effect at the tumor site make nanocatalytic systems a great advantages in the treatment of diseases. This paper firstly outlines the progress of the research on bio-nanostructured nanoenzyme catalytic systems in disease diagnosis and treatment， followed by a detailed review of the catalytic mechanisms of natural enzymes， mimetic enzymes， and cascade enzyme systems. The application of nanoenzyme catalytic systems in bioimaging and their pathways of action in related metabolic diseases were introduced. Finally， the outlook on the development of nanoenzyme catalytic systems for bio diagnosis and treatment was proposed.



Design and Applications of Hypoxia Optical Probes

LI Cheng, ZHOU Sensen, JIANG Xiqun

2022, 43(12):  20220558.  doi:10.7503/cjcu20220558

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Oxygen plays an important role in life activities and provides an important source of energy for aerobic organisms. Insufficient oxygen supply will lead to tissue hypoxia. Hypoxia is often closely related to inflammation， chronic wounds， tumors and other diseases， and tissue oxygen concentration is also an important basis for evaluating body health. The enormous advantages of optical imaging in terms of spatial resolution， sensitivity and cost-effectiveness make it an important imaging diagnostic tool for inflammation， cancer， brain diseases， and surgical navigation. In this review， we introduce the synthesis strategies of several hypoxia-responsive optical probes and illustrate the applications of different hypoxia optical probes in tumor detection， inflammation monitoring， wound oxygen content imaging， treatment response monitoring and food packaging. Finally， we discussed the application prospect of hypoxia optical imaging.



Synchrotron-based X-ray Microscopy for Brain Imaging

TANG Qiaowei, CAI Xiaoqing, LI Jiang, ZHU Ying, WANG Lihua, TIAN Yang, FAN Chunhai, HU Jun

2022, 43(12):  20220379.  doi:10.7503/cjcu20220379

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The diagnosis and treatment of brain diseases， the exploration of advanced brain function mechanisms and the understanding of the origin of consciousness are of great significance to brain research. Imaging techniques have played an important role in elucidating the structure and function of the nervous system in brain science. So far， magnetic resonance imaging， optical imaging and electron microscopy imaging have provided powerful means for brain research and have made outstanding progress. Synchrotron-based X-ray microscopy imaging technology has the advantages of high resolution， fast imaging speed， and high penetration depth. It is a new type of brain imaging technology that complements existing technologies. In this review， we first briefly introduce the application of imaging techniques such as magnetic resonance imaging， optical imaging and electron microscopy imaging in the field of brain imaging， and focuse on the advantages of synchrotron-based X-ray microscopy and its application in brain structure and function imaging. On this basis， we propose the future development direction of the application of synchrotron-based X-ray microscopy in brain research， and discuss the advantages and feasibility of this technology in mapping human brain connectivity.



Diagnostic Imaging and Therapeutic Effects of Nanocatalysts by Intracellular in situ Catalytic Reactions

ZHANG Endong, LYU Fengting, HUANG Yiming, BAI Haotian, WANG Shu

2022, 43(12):  20220676.  doi:10.7503/cjcu20220676

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Nanocatalysts offer possibilities to realize intracellular in situ catalytic reactions for artificially regulating cellular activities at the molecular level. Artificial nanocatalysts have shown excellent catalytic performances in diagnostic imaging and treatment under different physiological and pathological conditions due to their low cost， good stability， and safe yield production. In this review， we summarized the key progress in nanocatalysts with the activities of natural enzymes for cancer and oxidative stress treatments， and the proposed concept of accurate diag⁃nostic imaging based on nanocatalyst-mediated intracellular catalytic reaction， as well as the challenges and prospects of nanocatalysts for further applications in the health care field were discussed.



Difluoromethyl Radical Reaction and Its Application in ¹⁸F-Labeling

LI Jiahao, LIANG Weiqiu, MU Boshuai, LIU Zhibo

2022, 43(12):  20220652.  doi:10.7503/cjcu20220652

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With the progress of positron emission tomography（PET）， the study of efficient ¹⁸F-labeling reactions is of great value. Meanwhile， with the rapid development of organic fluorine chemistry， researchers have developed a series of reagents as C1 synthons to yield difluoromethyl radical（·CHF₂）， which can be introduced into the ¹⁸F- labeling reactions. In this review， we analyzed from the perspective of chemical principles and summarized the recent studies on ·CHF₂ synthons， C—H bond activation and related ¹⁸F-labeling reactions. Furthermore， the research trends and hotspots were discussed.



Advances of Optical Probes in Atherosclerosis Imaging

YE Zhuo, JI Moxuan, LIU Dingbin

2022, 43(12):  20220556.  doi:10.7503/cjcu20220556

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Cardiovascular disease（CVD） is the leading cause of death worldwide. Atherosclerosis（AS） is the primary risk factor for all kinds of CVD， and its occurrence and development usually undergo a continuous chronic inflammatory process. Therefore， timely and efficient detection of AS has important clinical significance for early evaluation， diagnosis and treatment of CVD. Optical probes are widely used in biomedical detection and imaging because of their high sensitivity and spatial resolution as well as its ultra-fast signal acquisition and processing speed. This paper reviewed six common optical probes for AS imaging， involving small-molecule fluorescent probes， aggregate-induced emission（AIE） nanoprobes， quantum dot probes， upconversion nanoprobes， photoacoustic probes， and multi-modal probes. The advantages and disadvantages of various probes were also comparably analyzed. Based on this， we prospected the development prospects of optical probes in the field of AS imaging and put forward four suggestions.



Recent Advances in Lipid-responsive Probes in the Imaging and Treatment of Atherosclerosis

XU Xinyu, ZHANG Letian, CAO Hui, MA Yuan, LIU Liuhui, SONG Guosheng, ZHANG Xiaobing

2022, 43(12):  20220383.  doi:10.7503/cjcu20220383

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Atherosclerosis（AS） is one of the main threats of cardiovascular diseases（CVDs） and may lead to a series of serious adverse consequences such as acute coronary syndromes（e.g.， acute myocardial infarction）， stroke， and even sudden death. Abnormal accumulation of lipids is one of the signatures of AS， and it is necessary to observe their quantity， localization， and distribution in vivo. Fluorescent probes with the advantages of high operability， high spatial and temporal resolution， and good biocompatibility are expected to be favorable tools for understanding lipid function in AS. This review summarizes lipid droplet（LD）-specific optical imaging probes based on organic framework structures such as rhodamine， coumarin， dipyrromethene boron difluoride（BODIPY）， 1，8-naphthalimide， and metal complex probes， and highlights their applications in atherosclerotic plaque imaging， imaging-guided surgery and therapy. Finally， a summary and outlook on the field are presented， hoping to provide useful references for related research.



Cellular Endogenous Molecule-assisted Fluorescence Signal Amplification Strategy and the Application of Cell Imaging

MA Xiaofei, HU Shan, LI Junbin, YANG Sheng, CHEN Weiju, QING Zhihe, ZHOU Yibo, YANG Ronghua

2022, 43(12):  20220320.  doi:10.7503/cjcu20220320

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In situ signal amplification strategy is an effective mean to detect low-abundance of endogenous targets. However， most of signal amplification strategies rely on exogenous substances， which inevitably change the intracellular microenvironment and causing certain interference to the body. For this problem， it has been reported that using endogenous substances， such as metal ions， nucleic acids and proteases， can achieve in situ fluorescence signal amplification. Fluorescence imaging of different biomarkers is of great significance for the imaging of low-abundance target molecules. In this review， we summarize the related researches on endogenous substance-assisted signal amplification and the application of cell imaging. Firstly， we introduce endogenous nucleic acid， enzyme， protein， ATP and metal ion-assisted signal amplification strategies and discuss their signal amplification mechanisms. Then， the research progress of endogenous substance-assisted signal amplification probes in the detection and imaging of low-abundance substances was summarized. Finally， we look forward to the advantages and application prospects of this strategy in cell imaging.



Recent Development of Magnetic Particle Imaging Tracers

ZHANG Qingpeng, GUAN Guoqiang, LIU Huiyi, LU Chang, ZHOU Ying, SONG Guosheng

2022, 43(12):  20220375.  doi:10.7503/cjcu20220375

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Magnetic particle imaging（MPI） is a tracer method based on functional and tomography imaging techniques to detect the spatial distribution of magnetic nanoparticles（MNPs）， the contrast of positive signal， low background， infinite tissue penetration depth， non-invasive imaging as well as the advantages of no ionizing radiation， which is a promising biomedical imaging technology in recent years. The MPI signal is generated by switching the magnetic spin vector of MNPs at field-free points（FFP）. The imaging sensitivity and spatial resolution of MPI are highly dependent on the magnetic properties of MNPs themselves as MPI tracers， so the current research is mainly focused on the design and synthesis of MNPs. This review focuses on the latest research progress of MPI tracers， and summarizes the types， synthesis methods， properties and biomedical applications of MNPs that can be used as MPI tracers， in order to provide reference for the future development of MPI.



Silicon-based Nanoprobes for Imaging Detection and Therapy of Ocular Diseases

CHU Binbin, HE Yao

2022, 43(12):  20220546.  doi:10.7503/cjcu20220546

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Rapid and effective diagnosis and treatment are critical for alleviating the hazards caused by ocular diseases. Taking advantages of their attractive merits including small dimensions， large ratios of surface-to-volume， good surface tailorability， and unique optical/electronic/mechanic properties， numerous kinds of nanomaterials have been utilized to construct high-performance nanoprobes. Of particular note， during the past decade， silicon nanomaterials featuring favorable biocompatibility have been explored as multifunctional nanoprobes for the high-efficacy detection and therapy of different ocular diseases. Herein， we intend to summarize recent achievements in silicon-based nanoprobes for diagnosing and curing ocular diseases， such as corneal diseases， retinal diseases and glaucoma. Firstly， we highlight the preparation of silicon-based nanoprobes and their biomedical applications in the detection and treatment of corneal diseases［e. g.， corneal neovascularization（NV） and bacterial keratitis］. Secondly， we concentrate on the latest typical advancements of the synthesis and functionalization of silicon-based drug delivery systems， capable of imaging and treating retinal diseases（e.g.， retinitis pigmentosa and retinal NV）. Thirdly， we briefly outline the developments of multifunctional silicon-based drug delivery nanosystems and their in vivo bioapplications in the imaging analysis and treatments of glaucoma. In the final section， we further discuss the major challenges and prospects of silicon-based nanoprobes applying in the field of ocular diseases.



Recent Advances in the Development of Molecular Probes for Targeting Carbonic Anhydrases

YANG Yanling, YE Deju

2022, 43(12):  20220557.  doi:10.7503/cjcu20220557

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Carbonic anhydrases（CAs） are a class of enzymes， which are over-expressed in many tumor cells， participating in the regulation of hypoxic and acidic tumor microenvironments. CAs have become as an important type of targets for tumor diagnosis and treatment. Here， we briefly introduced the biological functions of CAs， and summarized the recent advances in the development of CAs-targeting molecular probes for tumor imaging and therapy. Moreover， the current challenges and perspectives in designing new CAs-targeted probes for cancer theranostics were also discussed.



Probe Design Strategies for Cy7-type Cyanine Dyes

QIN Wenjie, HUANG Yizhuo, LUO Xiao, QIAN Xuhong, YANG Youjun

2022, 43(12):  20220567.  doi:10.7503/cjcu20220567

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Cyanines， one of the most classic organic fluorophores， have find extensive applications in the fields of protein labelling， trace metal ion detection， biological relevant species sensing， in vitro and in vivo imaging， targeted cancer therapies owing to their excellent properties including large molar absorption coefficient， tunable wavelength， good solubility and biocompatibility. In recent years， biomedical researches demand deeper penetration depth for in vivo structural and functional imaging， thus the development of near infrared molecular probes based on excellent long-wavelength scaffolds has become an important research area with profound implications. Indole heptamethine cyanine（Cy7） is one of the most representative cyanine dyes. In this review， emphasis was primarily paid to the Cy7-based molecular probes since 1992. We hope this will delineate the design rationale and inspire the development of more Cy7-based probes.



Nucleic Acids-encoded Amplification for Single-cell Imaging

ZHAO Xueqi, ZHAO Yue, XUE Jing, BAI Min, CHEN Feng, SUN Ying, SONG Daqian, ZHAO Yongxi

2022, 43(12):  20220572.  doi:10.7503/cjcu20220572

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Single-cell imaging is of great significance in the field of life science and clinical medicine for its application on visualizing and quantifying of targets in single cells. Nucleic acids-encoded amplification converts targets to nucleic acids barcodes through specific molecular reactions， which is easy to achieve signal amplification. Due to its variety of probes， ease of programming， mild reaction conditions and high amplification efficiency， nucleic acids- encoded amplification emerges outstanding performance on sensitive and multiplexed imaging of various targets with low abundance in single cells， emerging as a new strategy for understanding cell state and exploring life process. This paper reviews the research progress of nucleic acids-encoded amplification in the field of single-cell fluorescence imaging on the basis of the encoding methods， which systematically clarifies the characteristics of encoding and amplification methods for living cell imaging and in situ cell imaging. Finally， the challenges of multiplex detection in living cells and future perspectives of nucleic acids-encoded amplification are summarized and discussed.



Near-infrared-Ⅱ Fluorescence Imaging for Tumor Diagnosis and Therapy

WANG Shiqi, LUO Bowen, YU Jicheng, GU Zhen

2022, 43(12):  20220577.  doi:10.7503/cjcu20220577

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Due to the distinct advantages of deep tissue penetration and high spatial-temporal resolution， near- infrared-Ⅱ（NIR-Ⅱ， 1000—1700 nm） fluorescence imaging technology that developed rapidly in the last decade has attracted extensive attentions for its great potential in tumor diagnosis and therapy. In this review， we first illustrated the mechanism and advantages of fluorescence imaging in the NIR-Ⅱ window. Afterward， the current fluorophores were categorized according to chemical structures， and their properties were introduced respectively. We also highlighted the advances in the development of fluorescence probes and their applications in tumor detection， surgery resection and phototherapy. Finally， we discussed the limitations of current NIR-Ⅱ fluorescence probes and the challenges during clinical translation as well as prospects for future biomedical applications.



Recent Advances on Fluorescent Tracers for in vivo Real-time Monitoring Glomerular Filtration Rate

DING Yiru, ZHANG Chaoying, XIE Hexin

2022, 43(12):  20220686.  doi:10.7503/cjcu20220686

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Acute kidney injury（AKI） is a commonly encountered clinical acute disease. Monitoring glomerular filtration rate（GFR） with exogenous fluorescent tracers in a non-invasive and real-time manner is of high importance in clinical practice for timely understanding of renal function in susceptible patients. This paper gives a comprehensive review of recent advances on exogenous fluorescent tracers for in vivo monitoring of glomerular filtration rate， with particular focus on the design strategy of fluorescent tracers and their application on in vivo imaging， as well as the development of corresponding detection devices. In the last part， we discuss the challenges and the development prospect in this field.



Article

Novel Biodegradable Nanodrugs ZnO₂@Fe³⁺-TA@PVP for Chemodynamic Therapy

ZHOU Shijie, ZHAO Ying, NIU Rui, XU Bo, XUE Dongzhi, WANG Yinghui, ZHANG Hongjie

2022, 43(12):  20220554.  doi:10.7503/cjcu20220554

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A novel biodegradable nanodrugs ZnO₂@Fe³⁺-TA@PVP for further improving the treatment effect of chemodynamic therapy（CDT） was prepared. In the acidic tumor microenvironment， ZnO₂@Fe³⁺-TA@PVP could be degraded to Zn²⁺， Fe³⁺， tannic acid（TA） and H₂O₂， achieving H₂O₂ self-supply. Moreover， Fe³⁺ ions were further reduced to Fe²⁺ by TA， realizing the self-generation of Fe²⁺ in the tumor site. Fenton reaction occurred between Fe²⁺ and H₂O₂ to produce high toxic ·OH， which realized efficient CDT. Meanwhile， Zn²⁺ ions inhibited the mitochondrial electron transport chain（ETC） to promote the production of endogenous superoxide anion（·O{}_{\mathrm{2}}^{-}）， thus synergistically improving the therapeutic effect.



Small-molecule-based Thermosensitive Polymer Nanoparticles for NIR-Ⅱ Fluorescence Imaging and Photothermal Therapy

CHEN Shangyu, SHEN Qingming, SUN Pengfei, FAN Quli

2022, 43(12):  20220392.  doi:10.7503/cjcu20220392

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An organic small molecule 4，9-bis［5-（9H-fluoren-2-yl）thiophen-2-yl］-6'，7-diphenyl-［1，2，5］thiadiazolo［3，4-g］quinoxaline（TQF） was selected as a precursor， followed by chemical modification into a small molecular chain transfer agent—TQF-phenylthio chain transfer agent（CTA）， which enabled the reversible addition-fragmentation chain transfer polymerization（RAFT）. Then， the copolymer［TQF-P（NIPAAm-co-OEGMA）， abbreviated as TPNO］ with good water solubility and lower critical solution temperature（LCST） was synthesized by RAFT with TQF-CTA as the chain transfer agent， azobisisobutyronitrile as initiator， as well as thermosensitive N-isopropylacrylamide（NIPAAm） and hydrophilic oligoethylene glycol methacrylate（OEGMA） as the monomers. TPNO was directly dissolved in water to prepare the thermosensitive spherical nanoparticles TQNO NPs. The results showed that TQNO NPs exhibited an obvious particle size change and a significant fluorescence enhancement behavior（2.2 times） when the test temperature was greater than LCST（35 ℃）， and successfully achieved bright second near-infrared（NIR-Ⅱ） fluorescence imaging（FI） of blood vessels and tumors in living mice. Meanwhile， TQNO NPs displayed a good photothermal conversion efficiency（PCE=29.8%）， and the in vitro cell experiments had successfully proved its desirable photothermal therapy（PTT） effect.



CeO₂@montmorillonite Nanozyme for Crohn’s Disease Therapy

CHEN Xiwen, CHENG Chaoqun, CHENG Yuan, ZHAO Sheng, WEI Hui

2022, 43(12):  20220476.  doi:10.7503/cjcu20220476

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Inflammatory bowel disease（IBD） is a chronic， nonspecific disease that is refractory and therefore affects the normal life of patients to a great extent. Although the global incidence of this disease is increasing year by year， ideal therapeutic drugs are still lacking in clinical practice. Inspired by the antioxidant activity of natural enzymes in organisms， the therapeutic strategies of natural enzymes for inflammatory diseases have come into view. However， natural enzymes have the limitations of poor stability and high cost. Here， we loaded cerium oxide on a montmoril- lonite surface to obtain CeO₂@montmorillonite（CeO₂@MMT） nanozyme and verified that it has an excellent curative effect and universality in the treatment of Crohn’s disease（CD） through in vitro and in vivo experiments. CeO₂@MMT showed good superoxide dismutase- and catalase-like activity in vitro. Its negative charges enable it to target the positively charged intestinal inflammatory site and exert an anti-inflammatory effect at the focus. Thus， it showed obvious curative effects and excellent biosafety in the treatment of CD in mice， which broadened the spectrum of the application of nanozymes.



One-step High-throughput Controlled Preparation of Biocompatible Water/Water Microcapsules with Triggered Release

ZHAI Xiaowei, PAN Meidie, SHI Pan, ZHAO Peng, CHEN Dong

2022, 43(12):  20220460.  doi:10.7503/cjcu20220460

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Biocompatible water/water microcapsules are of great significance for drug delivery and medical therapy. In this paper， co-axial microfluidic devices were designed via the optimization by numerical simulations and the analysis of flow resistance to realize one-step high-throughput controlled preparation of water/water microcapsules with good uniformity， tunable size and shell thickness， and excellent biocompatibility. Specifically， the influences of device design， inner phase flow rate， outer phase flow rate， outer phase/air interfacial tension， inner phase/outer phase interfacial tension， inner phase viscosity and outer phase viscosity on the diameter and shell thickness of water/water microcapsules were systematically investigated by means of experiments and simulations. By carefully analyzing the flow resistance of microchannels， microfluidic devices were parallelly amplified to achieve high-throughput preparation of water/water microcapsules with controlled size. Biocompatible water/water microcapsules are ideal delivery vehicles for various actives， showing controlled pH-triggered release of encapsulated cargos， which pave the way for their practical applications.



Boronate-based ¹⁹F NMR/MRI Molecular Probe for Activatable Deep-tissue Imaging of Reactive Oxygen Species

LI Ao, LI Lingxuan, ZUO Cuicui, CHEN Chuankai, FAN Yifan, BU Yifan, LIN Hongyu, GAO Jinhao

2022, 43(12):  20220545.  doi:10.7503/cjcu20220545

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Reactive oxygen species（ROS）， such as hydrogen peroxide， are playing critical roles in various physiological and pathological processes of organisms. There is a close correlation between abnormal levels of ROS and disease conditions including inflammation， tumor， and organ injuries， which renders ROS detection attractive as an important tool for the research and diagnosis of these diseases. However， imaging ROS in deep tissues of living subjects remains challenging. In this paper， we report the development of an activatable ¹⁹F magnetic resonance imaging（MRI） probe（Gd-DPBF） for sensing and imaging of generic ROS in living mice. Gd-DPBF is composed of a gadolinium chelate and a fluorinated moiety via a ROS-responsive aromatic boronate linkage. The capacity of Gd-DPBF for visualizing generic ROS in deep tissues and in the tumors of living mice is validated by a series of ex vivo and in vivo imaging experiments， illustrating its promising potential for in-depth and background-free imaging of various ROS-related biological processes in living subjects.