Bioconjugate Chemistry最新文献

{"title":"In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe.","authors":"Zhan Si, Lulu Tian, Hongxin Zhou, Jiasheng Lin, Jun Zhou","doi":"10.1021/acs.bioconjchem.5c00128","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00128","url":null,"abstract":"<p><p>We aimed to evaluate the biodistribution and specificity of ⁶⁸Ga-DOTA-TAT and RHO-TAT using MGC-803 and HT-29 tumor cells as well as tumor-xenografted nude mice and to demonstrate its application in positron emission tomography (PET) imaging. The in vitro evaluation of ⁶⁸Ga-DOTA-TAT was assessed in MGC-803 and HT-29 cell lines, and the in vivo evaluation of ⁶⁸Ga-DOTA-TAT was also performed in mice bearing MGC-803 or HT-29 tumors, respectively. Fluorescence microscopy was also employed to evaluate the specificity of RHO-TAT in vitro in MGC-803 and HT-29 cells as well as ex vivo in tumor slices of the corresponding tumor models. The in vivo imaging differences between ⁶⁸Ga-DOTA-TAT and ¹⁸F-FDG in MGC-803 and HT-29 tumors were also studied. The biodistribution and micro-PET results demonstrated significant uptake of ⁶⁸Ga-DOTA-TAT in non-FDG-avid MGC-803 tumors, whereas there was negligible uptake in FDG-avid HT-29 tumors. RHO-TAT showed superior fluorescence microscopy imaging effects in MGC-803 cells and tumor slices but not in HT-29 cells and tumor slices, which were consistent with the in vivo results. ⁶⁸Ga-DOTA-TAT combined with ¹⁸F-FDG can be applied noninvasively in cancers with PET imaging for potential patient selection and stratification. We demonstrated a higher binding of ⁶⁸Ga-DOTA-TAT and RHO-TAT to MGC-803 cells as well as to non-FDG-avid MGC-803 xenografted tumors and a lower binding to HT-29 cells and FDG-avid xenografted tumors. These results suggest that TAT has the potential to be a ligand for targeting certain tumors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810197","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":"Discovery of a Novel ADC for Multifunctional Theranostics: From Vascular Normalization to Synergistic Therapy.","authors":"Yanchen Li, Jin Wang, Tingting Liu, Junyu Zhang, Yuanyuan Shan, Jie Zhang","doi":"10.1021/acs.bioconjchem.5c00116","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00116","url":null,"abstract":"<p><p>Previous studies have shown the potential of bevacizumab-based ADCs in tumor vascular normalization and chemotherapy synergies. Here, in order to improve the tumor treatment efficiency of ADC and further avoid drug resistance, we introduced the previously discovered photodynamic therapy group PDT into bevacizumab, which has high reactive oxygen generation efficiency and deep tissue penetration ability, and has surprising imaging effect on solid tumors. At the same time, doxorubicin, a chemotherapy drug molecule with strong cytotoxicity, has also been introduced to construct novel multifunctional integrated antibody-drug conjugates, Bevacizumab-DOX-PDT. It is proved that novel ADCs have the antigen-antibody binding ability similar to bevacizumab, while also possess strong antitumor activity and vascular normalization activity. In addition, it also showed great tracer ability for transplanted tumors. In summary, the novel ADC showed a surprising vascular normalization-chemotherapy-photodynamic synergistic therapeutic effect, which further enriched the expansion of vascular normalization in the field of new drug discovery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801980","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":"Mitigating Cannabidiol's Non-Selective Cytotoxicity via Subcellular Organelle Targeting: Exploring Mitochondrial Targeting Potential.","authors":"Genglian Liu, Ru Li, Jingwei Gao, Cong Lin, Hongyuan Li, Yinghua Peng, Hongshuang Wang, Xiaohui Wang","doi":"10.1021/acs.bioconjchem.5c00012","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00012","url":null,"abstract":"<p><p>Cannabidiol (CBD), a phytocannabinoid from <i>Cannabis sativa</i>, is renowned for its nonpsychoactive properties and therapeutic potential. However, its clinical application is limited by nonselective cytotoxicity, affecting microglia, oligodendrocytes, and other cells. To address this, subcellular organelle-targeting strategies were explored to minimize off-target effects and enhance CBD's therapeutic index. Three organelle-specific conjugates targeting mitochondria, endoplasmic reticulum, and lysosomes were synthesized. Among these, the mitochondria-targeting triphenylphosphonium (TPP)-modified CBD conjugates demonstrated reduced cytotoxicity and enhanced anti-inflammatory activity. Further optimization identified a four-carbon ether chain linker (<b>CBD-TPP-C4</b>) that increased antineuroinflammatory activity by 3-fold and reduced cytotoxicity by 1.6-fold, compared to unmodified CBD. <b>CBD-TPP-C4</b> also elevated mitochondrial ATP levels in vitro, improved mitochondrial morphology and locomotor function in <i>Caenorhabditis elegans</i>, and potentiated morphine analgesia in mice. These findings highlight subcellular targeting as a promising strategy to enhance CBD's safety and efficacy, paving the way for improved therapeutic applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801984","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":"<i>In Silico</i>-Driven THIOMAB Approach for Stable PROTAC Conjugates by Docking Payloads in Antibody Cavities.","authors":"Shiwei Song, Yahui Liu, Jiaqi Liu, Wanyi Tai","doi":"10.1021/acs.bioconjchem.4c00588","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00588","url":null,"abstract":"<p><p>The heterobifunctional proteolysis targeting chimeras (PROTACs) are a class of emerging therapeutic modalities that enable selective degradation of target proteins in cells. As antibody payloads, they offer several advantages compared to conventional chemical toxins, such as catalytic nature, potent and long-lasting activity, and precise selectivity to avoid systemic toxicity. However, the relatively large size and high hydrophobicity of these chimeric payloads may result in challenging the stability of antibodies, which complicates the in vivo performance. In this work, we use the highly hydrophobic GNE-987 as model PROTAC to evaluate a THIOMAB approach for mitigating the conjugate's hydrophobicity while maintaining the therapeutic potency. We describe an <i>in silico</i> method to select the less hydrophobic site in an antibody and employ the stable tetrapeptide-aminomethoxy linker to conjugate the PROTAC payloads. The resulting degrader-antibody conjugate (J591 DAC) displays antigen-dependent BRD4 degradation and potent cytotoxic activity in PSMA-positive cancer cells. Finally, this DAC, bearing two highly hydrophobic PROTACs, also exhibits a long blood retention and strong antitumor efficacy in mouse models, likely owing to the homogeneous and stable conjugation from the THIOMAB approach. This work provides an example of the design and construction of antibody conjugates with highly hydrophobic payloads.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801955","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":"Phototheranostic Zinc Porphyrin Nanoparticles Triggered by an 808 nm Laser: NIR-II Fluorescence/Photoacoustic Imaging-Guided Combined Photothermal/Photodynamic/NO Therapy","authors":"Hongyu Chen,&nbsp;Xiaobo Zhao*,&nbsp;Akbar Halimov,&nbsp;Mingkai Fu,&nbsp;Jing Tu,&nbsp;Hui Liu,&nbsp;Huajun Xu* and Jun Liu*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0008610.1021/acs.bioconjchem.5c00086","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00086https://doi.org/10.1021/acs.bioconjchem.5c00086","url":null,"abstract":"<p >Single-wavelength lasers that trigger intelligently designed multifunctional theranostic nanoplatforms are urgently needed for early cancer diagnosis and imaging-guided therapy. In this study, a novel zinc porphyrin, Por-TR, was fabricated by incorporating thiophene as a donor and introducing electron acceptors on both sides to expand the conjugation. The presence of multiple flexible chains in the molecular structure of Por-TR inhibits π–π stacking, which allows it to form J nanoaggregates when coassembled with DSPE-PEG2000, demonstrating maximum absorption at approximately 808 nm. These Por-TR NPs provide NIR-II fluorescence/PA dual-modal signals for imaging and serve as a combined PTT/PDT therapeutic agent, making them a suitable multifunctional theranostic nanoplatform. To further improve their therapeutic effects, we embedded a thermosensitive NO donor, BNN6, in the Por-TR nanosystem to achieve combined PDT/PTT/NO therapy. Intravenous injection of Por-TR-NO NPs into 4T1 tumor-bearing mice enabled the accurate observation of tumor location via NIR-II fluorescence/PA dual-modal imaging. In vivo therapy results show that the Por-TR-NO NPs exhibited remarkable antitumor efficacy in combined PTT/PDT/NO therapy, which was triggered by an 808 nm laser. Overall, this nanoplatform offers a versatile approach to cancer diagnosis and treatment.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 4","pages":"838–845 838–845"},"PeriodicalIF":4.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832624","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":"Phototheranostic Zinc Porphyrin Nanoparticles Triggered by an 808 nm Laser: NIR-II Fluorescence/Photoacoustic Imaging-Guided Combined Photothermal/Photodynamic/NO Therapy.","authors":"Hongyu Chen, Xiaobo Zhao, Akbar Halimov, Mingkai Fu, Jing Tu, Hui Liu, Huajun Xu, Jun Liu","doi":"10.1021/acs.bioconjchem.5c00086","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00086","url":null,"abstract":"<p><p>Single-wavelength lasers that trigger intelligently designed multifunctional theranostic nanoplatforms are urgently needed for early cancer diagnosis and imaging-guided therapy. In this study, a novel zinc porphyrin, Por-TR, was fabricated by incorporating thiophene as a donor and introducing electron acceptors on both sides to expand the conjugation. The presence of multiple flexible chains in the molecular structure of Por-TR inhibits π-π stacking, which allows it to form J nanoaggregates when coassembled with DSPE-PEG2000, demonstrating maximum absorption at approximately 808 nm. These Por-TR NPs provide NIR-II fluorescence/PA dual-modal signals for imaging and serve as a combined PTT/PDT therapeutic agent, making them a suitable multifunctional theranostic nanoplatform. To further improve their therapeutic effects, we embedded a thermosensitive NO donor, BNN6, in the Por-TR nanosystem to achieve combined PDT/PTT/NO therapy. Intravenous injection of Por-TR-NO NPs into 4T1 tumor-bearing mice enabled the accurate observation of tumor location via NIR-II fluorescence/PA dual-modal imaging. In vivo therapy results show that the Por-TR-NO NPs exhibited remarkable antitumor efficacy in combined PTT/PDT/NO therapy, which was triggered by an 808 nm laser. Overall, this nanoplatform offers a versatile approach to cancer diagnosis and treatment.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801989","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":"Mechanistic Characterization of the Potency of THIOMAB Antibody-Drug Conjugates Targeting <i>Staphylococcus aureus</i> and ETbR-Expressing Tumor Cells Using Quantitative LC-MS/MS Analysis of Intracellular Drug Accumulation.","authors":"Hilda Hernandez-Barry, Josefa Dela Cruz-Chuh, Kimberly K Kajihara, Jyoti Asundi, Richard Vandlen, Donglu Zhang, Wouter L W Hazenbos, Thomas Pillow, Yichin Liu, Cong Wu, Katherine R Kozak, Kelly M Loyet","doi":"10.1021/acs.bioconjchem.4c00533","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00533","url":null,"abstract":"<p><p>THIOMAB drug conjugate (TDC) technology provides site-specific conjugation of linker drugs to antibodies, allowing for targeted delivery of the payload. While a direct measurement of TDC cytotoxic potency allows efficient screening and confirmation that new drugs conjugated to antibodies result in proper processing in cells, additional mechanistic characterization is often needed to provide information-rich data to guide further optimization of TDC design. For example, a quantitative understanding of how TDCs are processed intracellularly can help determine which processing step is impacting payload delivery and thereby inform the basis of the TDC efficacy. Here, we measure the cellular accumulation of two different TDC drug payloads: MAPK (mitogen-activated protein kinase) pathway inhibitor targeting ETbR-expressing tumor cells and an antibiotic active against <i>Staphylococcus aureus</i> with an <i>in vitro</i> cell-based drug release LC-MS/MS assay in a 96-well format. This assay allowed us to correlate the cellular potency of each unconjugated molecule with the amount of payload that accumulated inside the cell. In the case of the pathway inhibitor drug, the biochemical characterization of TDC processing by cathepsin B and purified human liver enzyme extract demonstrated a correlation between the efficiency of the linker drug cleavage and intracellular payload accumulation. For the antibody-antibiotic conjugate, kinetic analysis of intracellular free drug retention provided valuable insight into the chemistry modifications needed for an efficient TDC. Taken together, we demonstrated the utility of quantitative LC-MS/MS assays as one tool in guiding the design of more effective TDCs via the mechanistic release characterization of two distinct payloads.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778586","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":"Mechanistic Characterization of the Potency of THIOMAB Antibody–Drug Conjugates Targeting Staphylococcus aureus and ETbR-Expressing Tumor Cells Using Quantitative LC-MS/MS Analysis of Intracellular Drug Accumulation","authors":"Hilda Hernandez-Barry,&nbsp;Josefa dela Cruz-Chuh,&nbsp;Kimberly K. Kajihara,&nbsp;Jyoti Asundi,&nbsp;Richard Vandlen,&nbsp;Donglu Zhang,&nbsp;Wouter L.W. Hazenbos,&nbsp;Thomas Pillow,&nbsp;Yichin Liu,&nbsp;Cong Wu,&nbsp;Katherine R. Kozak and Kelly M. Loyet*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0053310.1021/acs.bioconjchem.4c00533","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00533https://doi.org/10.1021/acs.bioconjchem.4c00533","url":null,"abstract":"<p >THIOMAB drug conjugate (TDC) technology provides site-specific conjugation of linker drugs to antibodies, allowing for targeted delivery of the payload. While a direct measurement of TDC cytotoxic potency allows efficient screening and confirmation that new drugs conjugated to antibodies result in proper processing in cells, additional mechanistic characterization is often needed to provide information-rich data to guide further optimization of TDC design. For example, a quantitative understanding of how TDCs are processed intracellularly can help determine which processing step is impacting payload delivery and thereby inform the basis of the TDC efficacy. Here, we measure the cellular accumulation of two different TDC drug payloads: MAPK (mitogen-activated protein kinase) pathway inhibitor targeting ETbR-expressing tumor cells and an antibiotic active against <i>Staphylococcus aureus</i> with an <i>in vitro</i> cell-based drug release LC-MS/MS assay in a 96-well format. This assay allowed us to correlate the cellular potency of each unconjugated molecule with the amount of payload that accumulated inside the cell. In the case of the pathway inhibitor drug, the biochemical characterization of TDC processing by cathepsin B and purified human liver enzyme extract demonstrated a correlation between the efficiency of the linker drug cleavage and intracellular payload accumulation. For the antibody–antibiotic conjugate, kinetic analysis of intracellular free drug retention provided valuable insight into the chemistry modifications needed for an efficient TDC. Taken together, we demonstrated the utility of quantitative LC-MS/MS assays as one tool in guiding the design of more effective TDCs via the mechanistic release characterization of two distinct payloads.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 4","pages":"652–661 652–661"},"PeriodicalIF":4.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832969","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":"Fc Multisite Conjugation and Prolonged Delivery of the Folate-Targeted Drug Conjugate EC140","authors":"Yan Zheng,&nbsp;Hong Cheng,&nbsp;Sibo Jiang and Wanyi Tai*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0003710.1021/acs.bioconjchem.5c00037","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00037https://doi.org/10.1021/acs.bioconjchem.5c00037","url":null,"abstract":"<p >Small molecule-drug conjugate (SMDC) is a targeted drug delivery technology that develops in parallel with the antibody-drug conjugate. However, the clinical translation of SMDC faces challenges due to its limited circulating half-life in vivo. The drawback in pharmacokinetics is that it restricts the exposure time of SMDC to tumor tissues and ultimately reduces the therapeutic efficacy. In this study, we chemically conjugated a folate-targeted SMDC EC140 to the long-circulating Fc protein at multiple sites, yielding a stable and high-DAR Fc-SMDC conjugate (Fc-EC140). Fc-EC140 can bear approximately 4 molecules of EC140 per Fc protein (drug-antibody ratio = 4.1) and display enhanced potency in folate receptor (FR)-positive tumor cells compared to the SMDC comparator. In addition, Fc-EC140 retains the FcRn-mediated recycling function and displays an extended half-life of 28 h in the mice. In vivo, antitumor experiments demonstrate that intravenous administration of Fc-EC140 (Q7D × 3 at a dose of 15 mg/kg) nearly cures the KB tumors, which is far more effective than the comparator EC140 administrated at equivalent doses. This study presents a new strategy for the targeted delivery of SMDC.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 4","pages":"762–769 762–769"},"PeriodicalIF":4.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832604","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":"Fc Multisite Conjugation and Prolonged Delivery of the Folate-Targeted Drug Conjugate EC140.","authors":"Yan Zheng, Hong Cheng, Sibo Jiang, Wanyi Tai","doi":"10.1021/acs.bioconjchem.5c00037","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00037","url":null,"abstract":"<p><p>Small molecule-drug conjugate (SMDC) is a targeted drug delivery technology that develops in parallel with the antibody-drug conjugate. However, the clinical translation of SMDC faces challenges due to its limited circulating half-life in vivo. The drawback in pharmacokinetics is that it restricts the exposure time of SMDC to tumor tissues and ultimately reduces the therapeutic efficacy. In this study, we chemically conjugated a folate-targeted SMDC EC140 to the long-circulating Fc protein at multiple sites, yielding a stable and high-DAR Fc-SMDC conjugate (Fc-EC140). Fc-EC140 can bear approximately 4 molecules of EC140 per Fc protein (drug-antibody ratio = 4.1) and display enhanced potency in folate receptor (FR)-positive tumor cells compared to the SMDC comparator. In addition, Fc-EC140 retains the FcRn-mediated recycling function and displays an extended half-life of 28 h in the mice. In vivo, antitumor experiments demonstrate that intravenous administration of Fc-EC140 (Q7D × 3 at a dose of 15 mg/kg) nearly cures the KB tumors, which is far more effective than the comparator EC140 administrated at equivalent doses. This study presents a new strategy for the targeted delivery of SMDC.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770720","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}