Karla Lambaren, Noah Trac, Daniel Fehrenbach, Meena Madhur, Eun Ji Chung
{"title":"T Cell-Targeting Nanotherapies for Atherosclerosis.","authors":"Karla Lambaren, Noah Trac, Daniel Fehrenbach, Meena Madhur, Eun Ji Chung","doi":"10.1021/acs.bioconjchem.4c00590","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00590","url":null,"abstract":"<p><p>Cardiovascular diseases remain the leading cause of mortality worldwide. Specifically, atherosclerosis is a primary cause of acute cardiac events. However, current therapies mainly focus on lipid-lowering versus addressing the underlying inflammatory response that leads to its development and progression. Nanoparticle-mediated drug delivery offers a promising approach for targeting and regulating these inflammatory responses. In atherosclerotic lesions, inflammatory cascades result in increased T helper (Th) 1 and Th17 activity and reduced T regulatory activation. The regulation of T cell responses is critical in preventing the inflammatory imbalance in atherosclerosis, making them a key therapeutic target for nanotherapy to achieve precise atherosclerosis treatment. By functionalizing nanoparticles with targeting modalities, therapeutic agents can be delivered specifically to immune cells in atherosclerotic lesions. In this Review, we outline the role of T cells in atherosclerosis, examine current nanotherapeutic strategies for targeting T cells and modulating their differentiation, and provide perspectives for the development of nanoparticles specifically tailored to target T cells for the treatment of atherosclerosis.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466434","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}
Maria Nerantzaki, Claire Husser, Isaure Sergent, Laurence Charles, Jean-François Lutz, Michael Ryckelynck
{"title":"Chemical Synthesis and Poly(ethylene glycol)-Like Conjugation of the Mango-II Fluorogenic RNA Aptamer.","authors":"Maria Nerantzaki, Claire Husser, Isaure Sergent, Laurence Charles, Jean-François Lutz, Michael Ryckelynck","doi":"10.1021/acs.bioconjchem.4c00540","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00540","url":null,"abstract":"<p><p>A reliable method for the efficient chemical synthesis and poly(ethylene glycol) PEG-like modification of fluorogenic RNA aptamers is reported. The 43-mer version of Mango-II RNA (MangoII-v1), which binds tightly and specifically to the green fluorophore TO1-Biotin (TO1-B), was synthesized by automated phosphoramidite chemistry using 2'-<i>O</i>-[(triisopropylsilyl)oxy]methyl] (2'-<i>O</i>-TOM)-protected ribonucleosides. Solid-phase phosphoramidite chemistry was also used as a single tool to prepare MangoII-v1 modified with a PEG-like oligophosphate synthetic segment (MangoII-v1-<b>P</b>). After cleavage from the resin, deprotection, and purification, the capacity to activate the fluorescence of TO1-B and the degradation behavior of the chemically synthesized RNAs MangoII-v1 and MangoII-v1-<b>P</b>, were deeply investigated in comparison with those of the enzymatically synthesized 48 nucleotides long RNA MangoII. Interestingly, the chemically synthesized MangoII-v1 RNA aptamer demonstrated great activity toward its target, compared to the enzymatically synthesized analogue. Moreover, it was found to be highly stable, retaining its structural integrity and bioactivity, even after seven days of incubation in 20% fetal bovine serum. MangoII-v1-<b>P</b> also showed a high affinity for TO1-B and excellent degradation resistance.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466422","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}
Steven E Caldwell, Isabella R Demyan, Gianna N Falcone, Avani Parikh, Jason Lohmueller, Alexander Deiters
{"title":"Conditional Control of Benzylguanine Reaction with the Self-Labeling SNAP-tag Protein.","authors":"Steven E Caldwell, Isabella R Demyan, Gianna N Falcone, Avani Parikh, Jason Lohmueller, Alexander Deiters","doi":"10.1021/acs.bioconjchem.5c00002","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00002","url":null,"abstract":"<p><p>SNAP-tag, a mutant of the O<sup>6</sup>-alkylguanine-DNA-alkyltransferase, self-labels by reacting with benzylguanine (BG) substrates, thereby forming a thioether bond. SNAP-tag has been genetically fused to a wide range of proteins of interest in order to covalently modify them. In the context of both diagnostic and therapeutic applications, as well as use as a biological recording device, precise control in a spatial and temporal fashion over the covalent bond-forming reaction is desired to direct inputs, readouts, or therapeutic actions to specific locations, at specific time points, in cells and organisms. Here, we introduce a comprehensive suite of six caged BG molecules: one light-triggered and five others that can be activated through various chemical and biochemical stimuli, such as small molecules, transition metal catalysts, reactive oxygen species, and enzymes. These molecules are unable to react with SNAP-tag until the trigger is present, which leads to near complete SNAP-tag conjugation, as illustrated both in biochemical assays and on human cell surfaces. This approach holds promise for targeted therapeutic assembly at disease sites, offering the potential to reduce off-target effects and toxicity through precise trigger titration.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466431","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}
Jing Wang, Chengxue He, Rui Guo, Li Wen, Jinping Tao, Huimao Zhang, HaiFeng Huang, Hua Zhu, Zhi Yang, Xianteng Yang
{"title":"[<sup>177</sup>Lu]Lu-XYIMSR-01: A Novel CAIX-Targeted Radiotherapeutic for Enhanced Treatment of Malignant Glioma.","authors":"Jing Wang, Chengxue He, Rui Guo, Li Wen, Jinping Tao, Huimao Zhang, HaiFeng Huang, Hua Zhu, Zhi Yang, Xianteng Yang","doi":"10.1021/acs.bioconjchem.5c00041","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00041","url":null,"abstract":"<p><p>Malignant glioma highly expresses carbonic anhydrase IX (CAIX). This study aimed to develop [<sup>177</sup>Lu]Lu-XYIMSR-01, a small-molecule therapeutic agent CAIX, to assess its potential for treating malignant glioma. [<sup>177</sup>Lu]Lu-XYIMSR-01 was synthesized by radiolabeling DOTA-XYIMSR-01 with <sup>177</sup>Lu. In vitro assays were conducted to evaluate the affinity for U87MG tumor cells. The probe was injected via the tail vein into subcutaneous and orthotopic U87MG models for micro-SPECT/CT imaging. The survival rates of tumor-bearing mice were assessed after [<sup>177</sup>Lu]Lu-XYIMSR-01 injection by intratumoral in orthotopic models, including untreated controls and those treated with Temozolomide or combination therapy. After purification, the radiochemical yield of [<sup>177</sup>Lu]Lu-XYIMSR-01 was 86.47 ± 2.42%, with a radiochemical purity (RCP) of 99%. Its cell uptake in U87MG cells was 3.70 ± 0.57 ‰ AD/10<sup>5</sup> cells, significantly higher than that in HCT116 cells (0.68 ± 0.16 ‰ AD/10<sup>5</sup> cells, <i>P</i> = 0.001). In the biodistribution study, [<sup>177</sup>Lu]Lu-XYIMSR-01 uptake in U87MG tumors was 6.19 ± 1.37%ID/g, with a tumor/muscle ratio of 20.14 ± 3.24. In the orthotopic glioma model, local injection combined with Temozolomide significantly improved survival and inhibited tumor growth. The results indicate that [<sup>177</sup>Lu]Lu-XYIMSR-01 is a promising therapeutic molecular probe for targeting CAIX, and its combination with Temozolomide significantly enhances treatment outcomes for malignant glioma.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466677","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}
Bioconjugate ChemistryPub Date : 2025-02-19Epub Date: 2025-01-22DOI: 10.1021/acs.bioconjchem.4c00398
Christine S Nervig, Megan Rice, Marcello Marelli, R James Christie, Shawn C Owen
{"title":"Modular Synthesis of Anti-HER2 Dual-Drug Antibody-Drug Conjugates Demonstrating Improved Toxicity.","authors":"Christine S Nervig, Megan Rice, Marcello Marelli, R James Christie, Shawn C Owen","doi":"10.1021/acs.bioconjchem.4c00398","DOIUrl":"10.1021/acs.bioconjchem.4c00398","url":null,"abstract":"<p><p>Antibodies have gained clinical success in the last two decades for the targeted delivery of highly toxic small molecule chemotherapeutics. Yet antibody-drug conjugates (ADCs) often fail in the clinic due to the development of resistance. The delivery of two mechanistically distinct small molecule drugs on one antibody is of increasing interest to overcome these challenges with single-drug ADCs. We have developed a modular synthetic strategy for the construction of a library of 19 dual-drug ADCs where drugs are conjugated through unnatural cyclopentadiene-containing amino acids and native cysteine residues on an anti-HER2 trastuzumab scaffold. Importantly, this strategy utilizes the same functional group on the linker-drug construct; this allows for the facile addition of drugs at either conjugation site and enables the evaluation of different drug-to-antibody ratios and combinations of drug pairs. We tested the library on high- and mid-HER2 expressing cell lines and observed increased toxicity in several dual-drug ADCs compared with single-drug constructs. The strategy developed herein provides a method for the facile synthesis, characterization, and evaluation of dual-payload ADCs. Simultaneous delivery of combinations of drugs with distinct mechanisms of action is critical for the next generation of targeted drug delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"190-202"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996185","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":"PEGylation of Dipeptide Linker Improves Therapeutic Index and Pharmacokinetics of Antibody-Drug Conjugates.","authors":"Jing Long, Ting Shao, Yongmei Wang, Tianzhi Chen, Yuning Chen, Yi-Li Chen, Qi Wang, Xiong Yu, Jinghua Yu, Kaifeng He, Han-Bin Lin, Xingxing Diao, Guifeng Wang, Chunhe Wang","doi":"10.1021/acs.bioconjchem.4c00392","DOIUrl":"10.1021/acs.bioconjchem.4c00392","url":null,"abstract":"<p><p>Hydrophobic payloads incorporated into antibody-drug conjugates (ADCs) typically are superior to hydrophilic ones in tumor penetration and \"bystander killing\" upon release from ADCs. However, they are prone to aggregation and accelerated plasma clearance, which lead to reduced efficacies and increased toxicities of ADC molecules. Shielding the hydrophobicity of payloads by incorporating polyethylene glycol (PEG) elements or sugar groups into the ADC linkers has emerged as a viable alternative to directly adopting hydrophilic payloads. In this study, ADC linkers incorporating PEG or sugar groups were synthesized by modifying dipeptide linkers, with hydrophobic monomethyl auristatin E (MMAE) serving as an exemplary hydrophobic payload. All drug-linkers (DLs) were conjugated to RS7, a humanized antibody targeting Trop-2, with drug-to-antibody ratio (DAR) values set at 4 or 8. Among these, the ADC molecule RS7-DL 11, featuring a methyl-PEG<sub>24</sub> (mPEG<sub>24</sub>) moiety as a side chain to the Valine-Lysine-PAB (VK) linker, demonstrated maximum hydrophilicity, biophysical stability, and tumor suppression, along with prolonged half-life and enhanced animal tolerability. In conclusion, through PEGylation of the traditional dipeptide linker, we have demonstrated an optimized ADC conjugation technology that can be employed for conjugating ultrahydrophobic payloads, thus enhancing both the therapeutic index and pharmacokinetics profile.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"179-189"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996192","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}
Bioconjugate ChemistryPub Date : 2025-02-19Epub Date: 2025-01-09DOI: 10.1021/acs.bioconjchem.4c00454
Omri Shelef, Sara Gutkin, Molhm Nassir, Anne Krinsky, Ronit Satchi-Fainaro, Phil S Baran, Doron Shabat
{"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":"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":"152-159"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843602/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioconjugate ChemistryPub Date : 2025-02-19Epub Date: 2025-02-06DOI: 10.1021/acs.bioconjchem.4c00514
Jarrod P Cohen, Adam DiCaprio, Jian He, Mikhail Reibarkh, James Small, Matthew Schombs
{"title":"Method for Screening Sodium Cyanoborohydride for Free Cyanide Content and Its Impact on Bioconjugation Chemistry.","authors":"Jarrod P Cohen, Adam DiCaprio, Jian He, Mikhail Reibarkh, James Small, Matthew Schombs","doi":"10.1021/acs.bioconjchem.4c00514","DOIUrl":"10.1021/acs.bioconjchem.4c00514","url":null,"abstract":"<p><p>Sodium cyanoborohydride (CBH) is commonly used as a mild reducing agent in the reductive amination of aldehydes and free amines. Within the pharmaceutical industry, this reaction is employed in the bioconjugation of proteins and peptides. Free cyanide species such as HCN and NaCN are known residual impurities in CBH that can contribute to the formation of undesired side products including cyanoamines and cyanohydrins. In commercial processes, the potential for bound cyanated species requires an analytical control strategy to monitor and mitigate any risk to human health. Given these concerns, minimization of cyanated side products is of utmost priority and can be achieved through a robust control strategy of quantitative screening of starting materials for free cyanide. Alternative risk mitigation strategies such as purification of bound cyanide containing species to pure species are less effective due to minor chemical differences between the expected product and bound cyanide species. Herein, we present a simple chromatographic assay for the quantitation of free cyanide in the raw material sodium cyanoborohydride. Method development, robustness evaluation, and scientific soundness assessment are reported with excellent linearity, accuracy, precision, and specificity. Additionally, this method was applied for the evaluation of raw material supplied from 10 commercial sources, none of which report a specification for free cyanide within their certificate of analysis. The measured free cyanide from these vendors ranged from 8 to 80 mM concentration, thereby confirming the value of screening these raw materials. Finally, we demonstrate the impact of free cyanide on a model bioconjugation reaction between ornithine and glyceraldehyde.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"245-252"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioconjugate ChemistryPub Date : 2025-02-19Epub Date: 2025-02-04DOI: 10.1021/acs.bioconjchem.4c00595
Shivangi Kharbanda, Osaid Alkhamayseh, Georgia Eastham, Jimmie D Weaver
{"title":"Development of Transiently Strainable Benzocycloheptenes for Catalyst-Free, Visible-Light-Mediated [3 + 2]-Cycloadditions.","authors":"Shivangi Kharbanda, Osaid Alkhamayseh, Georgia Eastham, Jimmie D Weaver","doi":"10.1021/acs.bioconjchem.4c00595","DOIUrl":"10.1021/acs.bioconjchem.4c00595","url":null,"abstract":"<p><p>Dynamic photogeneration of ephemeral and reactive species is enabling for chemical reactions, providing spatial and temporal control. A previous study from our group established the ability of 6,7-dihydro-5H-benzo[7]annulene, benzocycloheptene (<b>BC7</b>), to convert photochemical energy into ring strain, enabling the rapid cycloaddition of alkyl azides with the reversibly formed and transient <i>trans</i>-isomer, affording versatile nonaromatic triazolines. Despite the conceptual advances of the previous study, some challenges remained: the fragility of the triazoline products, the low regioselectivity for the cycloaddition, a need for an iridium-based photosensitizer and organic-based solvents, and a lack of convenient linchpin functional group handles. Herein, we communicate the development of a second generation of <b>BC7</b> molecules that overcome the issues of the first generation. A method to convert fragile triazoline products to stable triazoles was developed. The alkene component was polarized with a carbonyl group, dramatically improving the regioselectivity while simultaneously red-shifting the absorbance of the cycloalkene into the visible region, which was expected to facilitate direct excitation and eliminate the need for photocatalysts. However, experiments indicated that the cycloaddition involved passage through a triplet manifold, complicating the direct excitation strategy. This was successfully overcome by attaching a bromine atom directly to the alkene moiety, which accelerated singlet-to-triplet intersystem crossing by the heavy atom effect. Further exploration identified sites of substitution that can increase the water solubility and provide a handle for the loading of chemical tools and probes.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"302-308"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}