Bioconjugate Chemistry最新文献

{"title":"Targeted NIR Fluorescent Mechanically Interlocked Molecules-Peptide Bioconjugate for Live Cancer Cells Submitochondrial Stimulated Emission Depletion Super-Resolution Microscopy.","authors":"Samiran Kar, Rabi Sankar Das, Tapas Bera, Shreya Das, Ayan Mukherjee, Aniruddha Mondal, Arunima Sengupta, Samit Guha","doi":"10.1021/acs.bioconjchem.4c00476","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00476","url":null,"abstract":"<p><p>Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed α_Vβ₃ integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP⁺ functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)₂-Mito-MIMs-TPP⁺ are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy. Water-soluble NIR (RGDS)₂-Mito-MIMs-TPP⁺ is an effective class of MIMs-peptide bioconjugate with promising photophysics; for instance, remarkable photostability and thermal stability, strong and narrow NIR abs/em bands with high quantum yield, ultrabrightness, decent fluorescence lifetime, reasonable stability against cellular nucleophiles, biocompatibility, noncytotoxicity, and dual-targeted living cancer cell submitochondrial imaging ability are all indispensable criteria for targeted super-resolved STED microscopy.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymidine Phosphodiester Chemiluminescent Probe for Sensitive and Selective Detection of Ectonucleotide Pyrophosphatase 1.","authors":"Omri Shelef, Sara Gutkin, Molhm Nassir, Anne Krinsky, Ronit Satchi-Fainaro, Phil S Baran, Doron Shabat","doi":"10.1021/acs.bioconjchem.4c00454","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00454","url":null,"abstract":"<p><p>ENPP-1 is a transmembrane enzyme involved in nucleotide metabolism, and its overexpression is associated with various cancers, making it a potential therapeutic target and biomarker for early tumor diagnosis. Current detection methods for ENPP-1 utilize a colorimetric probe, <b>TMP-</b><i><b>p</b></i><b>NP</b>, which has significant limitations in sensitivity. Here, we present probe <b>CL-ENPP-1</b>, the first nucleic acid-based chemiluminescent probe designed for rapid and highly sensitive detection of ENPP-1 activity. The design of probe <b>CL-ENPP-1</b> features a phenoxy-adamantyl-1,2-dioxetane luminophore linked to thymidine via a phosphodiesteric bond. Upon cleavage of the enzymatic substrate by ENPP-1, the probe undergoes an efficient chemiexcitation process to emit a green photon. Probe <b>CL-ENPP-1</b> demonstrates an exceptional signal-to-noise ratio of 15000 and a limit of detection value approximately 4500-fold lower than the widely used colorimetric probe <b>TMP-</b><i><b>p</b></i><b>NP</b>. A comparison of <b>TMP-</b><i><b>p</b></i><b>NP</b> activation by ENPP-1 versus alkaline phosphatase (ALP) reveals a complete lack of selectivity. Removal of the self-immolative spacer from probe <b>CL-ENPP-1</b> resulted in a new chemiluminescent probe, <b>CL-ENPP-2</b>, with an 18.4-fold increase in selectivity for ENPP-1 over ALP. The ability of probe <b>CL-ENPP-2</b> to detect ENPP-1 activity in mammalian cells was assessed using the human breast cancer cell line MDA-MB-231. This probe demonstrated a 19.5-fold improvement in the signal-to-noise ratio, highlighting its superior ability to detect ENPP-1 activity in a biological sample. As far as we know, to date, <b>CL-ENPP-1</b> and <b>CL-ENPP-2</b> are the most sensitive probes for the detection of ENPP-1 catalytic activity. We anticipate that our new chemiluminescent probes will be valuable for various applications requiring ENPP-1 detection, including enzyme inhibitor-based drug discovery assays. The insights gained from our probe design principles could advance the development of more selective probes for ENPP-1 and contribute to future innovations in chemiluminescence research.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-Specific Molecular Engineering of Nanobody-Glucoside Conjugates for Enhanced Brain Tumor Targeting.","authors":"Siyu Zhou, Xiaofeng Fang, Yunhe Luo, Yicheng Yang, Weijun Wei, Gang Huang, Xuanjun Zhang, Changfeng Wu","doi":"10.1021/acs.bioconjchem.4c00555","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00555","url":null,"abstract":"<p><p>Nanobodies play an increasingly prominent role in cancer imaging and therapy. However, their <i>in vivo</i> efficacy is often constrained by inadequate tumor penetration and rapid clearance from the bloodstream, particularly in brain tumors due to the intractable blood-brain barrier (BBB). Glycosylation is a favorable strategy for modulating the biological functions of nanobodies, including permeability and pharmacokinetics, but it also leads to heterogeneous glycan structures, which affect the targeting ability, stability, and quality of nanobodies. Here, we describe a post-translational modification strategy to produce precisely engineered and homogeneous nanobody-glucoside conjugates for effective BBB penetration and brain tumor targeting. Specifically, we employ an enzymatic method and click chemistry to functionalize nanobodies with glucoside and poly(ethylene glycol) (PEG), facilitating efficient transcytosis into the brain via glucose transporter-1 (GLUT1). Furthermore, we rationally select a near-infrared (NIR) fluorophore for labeling to maintain the metabolic pathway and biodistribution of nanobodies and assess their potency in two tumor models. The resulting nanobody-glucoside conjugates demonstrate a remarkable increase in BBB penetration and brain tumor accumulation, which are ∼2.9-fold higher in the transgenic mouse model and ∼5.7-fold higher in the orthotopic glioma model compared to unmodified nanobodies. This study provides a promising approach for the production of nanobody therapeutic agents for central nervous system (CNS) delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of the Size of Gold Nanoparticle Contrast Agents on CT Imaging of the Gastrointestinal Tract and Inflammatory Bowel Disease.","authors":"Derick N Rosario-Berríos, Amanda Pang, Leening P Liu, Portia S N Maidment, Johoon Kim, Seokyoung Yoon, Lenitza M Nieves, Katherine J Mossburg, Andrew Adezio, Peter B Noël, Elizabeth M Lennon, David P Cormode","doi":"10.1021/acs.bioconjchem.4c00507","DOIUrl":"10.1021/acs.bioconjchem.4c00507","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. Contrast agents that provide enhanced imaging performance are highly valuable in this field. Recent studies have made significant progress in developing better contrast agents for imaging the gastrointestinal tract using nanoparticles. However, the impact of nanoparticle size on this application remains unexplored. Gold nanoparticles (AuNPs) serve as an ideal model to investigate the effect of nanoparticle size on imaging of the gastrointestinal tract due to their controllable synthesis across a broad size range. In this study, we synthesized AuNPs with core sizes ranging from 5 to 75 nm to examine the effect of the size in this setting. AuNPs were coated with poly(ethylene glycol) (PEG) to enhance stability and biocompatibility. In vitro tests show that gold nanoparticles are cytocompatible with macrophage cells (∼100% cell viability) and remain stable under acidic conditions, with no significant size changes over time. Phantom imaging studies using a clinical CT scanner indicated that there was no effect of nanoparticle size on CT contrast production, as previously demonstrated. <i>In vivo</i> imaging using a mouse model of acute colitis revealed a strong contrast generation throughout the GI tract for all agents tested. For the most part, <i>in vivo</i> contrast was independent of AuNP size, although AuNP outperformed iopamidol (a clinically approved control agent). In addition, differences in attenuation trends were observed between healthy and colitis mice. We also observed almost complete clearance at 24 h of all formulations tested (less than 0.7% ID/g was retained), supporting their value as a model platform for studying nanoparticle behavior in imaging. In conclusion, this study highlights the potential of nanoparticles as effective contrast agents for CT imaging of the gastrointestinal tract (GIT) in the UC. Further systemic research is needed to explore contrast agents that can specifically image disease processes in this disease setting.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Irreversible Peptidomimetic Radioligand for PET Imaging of ST14 Protease.","authors":"Tukang Peng, Gang Huang, Haitao Zhao, Jianjun Liu","doi":"10.1021/acs.bioconjchem.4c00564","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00564","url":null,"abstract":"<p><p>To enhance the affinity of peptide ligands for their targets, covalent warheads can be engineered to facilitate irreversible binding. This study aimed at exploring the potential of a ⁶⁸Ga-labeled peptidomimetic radioligand, [⁶⁸Ga]Ga-DOTA-RQAR-kbt, for PET imaging through its irreversible binding to the suppression of tumorigenicity 14 (ST14). An Arg-Gln-Ala-Arg (RQAR) tetrapeptide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid for gallium-68 radiolabeling. The covalent warhead ketobenzothiazole was constructed as a serine trap for ST14 protease, resulting in the formation of DOTA-RQAR-kbt. We compared both the <i>in vitro</i> and <i>in vivo</i> properties of [⁶⁸Ga]Ga-DOTA-RQAR-kbt with those of its reversible-binding counterparts, [⁶⁸Ga]Ga-DOTA-RQAR-OH. DOTA-RQAR-kbt exhibits high affinity for ST14 and irreversibly binds to ST14, as evidenced by the lack of ST14 activity recovery following ultrafiltration. In contrast, DOTA-RQAR-OH shows reversible binding and has low affinity for ST14. PET/CT imaging confirmed the superior tumor targeting of [⁶⁸Ga]Ga-DOTA-RQAR-kbt compared to the [⁶⁸Ga]Ga-DOTA-RQAR-OH, with robust signals observed at 0.5, 1, and 2 h postinjection. Blocking studies underscored the probe's specificity, as they revealed a marked reduction in tumor uptake in the presence of excess RQAR-kbt. Biodistribution studies demonstrated significantly higher tumor uptake for [⁶⁸Ga]Ga-DOTA-RQAR-kbt, with 0.89 ± 0.03%ID/g at 1 h postinjection, which was reduced to 0.25 ± 0.03%ID/g (<i>P</i> < 0.01) in the presence of excess RQAR-kbt. In this proof-of-concept study, an irreversibly binding peptidomimetic radioligand targeting ST14 was evaluated, demonstrating improved tumor uptake <i>in vivo</i> compared with its reversibly binding counterparts. This approach holds promise for improving the potency of covalent radiotracers as PET agents.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorescence-Based Simple and Practical Assay Method for DNA Damage Analysis in DNA-Encoded Library Synthesis.","authors":"Seungyoon Kang, Gyung A Kim, Myo Naing Win, Yeongcheol Ki, Hohjai Lee, Min Su Han","doi":"10.1021/acs.bioconjchem.4c00483","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00483","url":null,"abstract":"<p><p>The dsDNA-selective fluorescent-dye-based DNA damage assay was developed for DNA-encoded library (DEL) synthesis. For the various DEL synthesis conditions, the assay was validated through cross-checking with high-performance liquid chromatography (HPLC) analysis, and the fact was confirmed that the usage of a specific ratio of organic solvent can critically induce DNA damage. Also, the applicability of the assay was confirmed through the screening of the DNA-damaging condition of the on-DNA amide coupling reaction and Pd-catalyzed on-DNA <i>N</i>-arylation reaction.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Through Physiological Barriers: Nanorobotic Strategies for Active Drug Delivery.","authors":"Meng Mao, Yingjie Wu, Qiang He","doi":"10.1021/acs.bioconjchem.4c00480","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00480","url":null,"abstract":"<p><p>Self-propelled micro/nanomotors (MNMs) represent a groundbreaking advancement in precision drug delivery, offering potential solutions to persistent challenges such as systemic toxicity, limited bioavailability, and nonspecific distribution. By transforming various energy sources into mechanical motion, MNMs are able to autonomously navigate through complex physiological environments, facilitating targeted delivery of therapeutic agents to previously inaccessible regions. However, to achieve efficient in vivo drug delivery, biomedical MNMs must demonstrate their ability to overcome crucial physiological barriers encompassing mucosal surfaces, blood flow dynamics, vascular endothelium, and cellular membrane. This review provides a comprehensive overview of the latest strategies developed to address these obstacles while also analyzing the broader challenges and opportunities associated with clinical translation. Our objective is to establish a solid foundation for future research in medical MNMs by focusing on enhancing drug delivery efficiency and advancing precision medicine, ultimately paving the way for practical theragnostic applications and wider clinical adoption.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule-Drug Conjugates Elicits Potent <i>In Vivo</i> Anticancer Activity.","authors":"Matilde Bocci, Lucrezia Principi, Ettore Gilardoni, Dario Neri, Samuele Cazzamalli, Andrea Galbiati","doi":"10.1021/acs.bioconjchem.4c00503","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00503","url":null,"abstract":"<p><p>OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment. In this work, we evaluate the use of monomethyl auristatin F (MMAF) as a payload, a close derivative of MMAE bearing a charged carboxylic acid that hampers its cellular permeability, typically employed in the development of internalizing antibody-drug conjugates. The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide Nanocarriers for Targeted Delivery of Nucleic Acids for Cancer Therapy.","authors":"Chunli Song, Leying Jiang, Xinrui Sha, Zijun Jiao, Yun Xing, Xi Li, Xinyu Li, Zhiyong Yao, Zigang Li, Dongyuan Wang, Lixiang Zhang, Yaping Zhang, Feng Yin","doi":"10.1021/acs.bioconjchem.4c00324","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00324","url":null,"abstract":"<p><p>Peptides have been extensively studied in nanomedicine with great bioactivity and biocompatibility; however, their poor cell-membrane-penetrating properties and nonselectivity greatly limit their clinical applications. In this study, tumor-targeting therapy was achieved by modifying our previously developed efficient peptide vector with the cancer-targeting peptide RGD, enabling it to specifically target tumor cells with a high expression of RGD-binding receptors. B-cell lymphoma-2 antisense oligonucleotides were selected as the target model to validate the effectiveness of the delivery carriers. Results demonstrated that this delivery system can be efficiently and selectively taken up by RGD receptor-positive cells (α_vβ₃ integrin receptor), further inducing effective target gene knockdown. Overall, this system provided a promising strategy for the targeted delivery of nucleic acid drugs.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Chemoinformatic-Guided Synthesis of a Spleen-Expressing mRNA Lipid Nanoparticle Platform.","authors":"Eshan A Narasipura, Yutian Ma, Palas Balakdas Tiwade, Rachel VanKeulen-Miller, Vincent Fung, Owen S Fenton","doi":"10.1021/acs.bioconjchem.4c00419","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00419","url":null,"abstract":"<p><p>mRNA lipid nanoparticles (LNPs) are a powerful technology that are actively being investigated for their ability to prevent, treat, and study disease. However, a major limitation remains: achieving extrahepatic mRNA expression. The development of new carriers could enable the expression of mRNA in non-liver targets, thus expanding the utility of mRNA-based medicines. In this study, we use a combination of chemoinformatic-guided material synthesis and design of experiment optimization for the development of a spleen-expressing lipid nanoparticle (SE-LNP). We begin with the synthesis of a novel cholesterol derivative followed by SE-LNP formulation and design of experiment-guided optimization to identify three lead SE-LNPs. We then evaluate their <i>in vitro</i> delivery mechanism, <i>in vivo</i> biodistribution, and protein expression in mice, ultimately achieving spleen-preferential expression. The goal of this paper is thus to create LNPs that preferentially express mRNA in the spleen upon intravenous delivery, demonstrating the potential of LNPs to modulate gene expression in extrahepatic tissues for disease treatment.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}