Bioconjugate Chemistry最新文献

{"title":"Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3'-DNA-Histone Cross-Links.","authors":"Yangxue Liu, Ying Peng, Zhishuo Wang, Xiaoying Wei, Kun Yang","doi":"10.1021/acs.bioconjchem.4c00453","DOIUrl":"10.1021/acs.bioconjchem.4c00453","url":null,"abstract":"<p><p>Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position. Using this method, we synthesized a hydrolytically stable and site-specific 3'-DNA-histone cross-link derived from an abasic DNA lesion. Such an adduct can be efficiently repaired by proteolysis coupled with nuclease excision. This work provides a strategy that can be readily expanded to synthesize DNA-histone cross-links derived from other aldehyde-containing DNA modifications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1883-1887"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638015","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":"Pharmacokinetic Positron Emission Tomography Imaging of an Optimized CD38-Targeted ⁶⁸Ga-Labeled Peptide in Multiple Myeloma: A Pilot Study.","authors":"Qi Yang, Lele Song, Zhao Chen, Yongkang Qiu, Tianyao Wang, Xinyao Sun, Wenpeng Huang, Cuicui Li, Zihua Wang, Lei Kang","doi":"10.1021/acs.bioconjchem.4c00497","DOIUrl":"10.1021/acs.bioconjchem.4c00497","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable disease characterized by its clinical and prognostic heterogeneity. Despite conventional chemotherapy and autologous hematopoietic stem cell transplantation, the management of relapsed and refractory MM disease poses significant challenges, both medically and socioeconomically. CD38, highly expressed on the surface of MM cells, serves as a distinct tumor biological target in MM. Peptides offer advantages over antibodies, enabling precise tumor imaging and facilitating early tumor diagnosis and dynamic immunotherapy monitoring. In this study, we developed PF381, a CD38-targeted peptide, and investigated its role in diagnosis, biodistribution, and dosimetry through ⁶⁸Ga-labeling for preclinical evaluation in tumor-bearing models. We screened a microchip-based combinatorial chemistry peptide library to obtain the amino acid sequence of PF381. Affinity for human CD38 was evaluated by SPRi. PF381 was conjugated with DOTA for radiolabeling with ⁶⁸Ga, and the complex was characterized by HPLC. PET imaging was performed in murine tumor models after the administration of [⁶⁸Ga]Ga-DOTA-PF381. Biodistribution analysis compared CD38-positive H929 and CD38-negative U266 tumors, and human radiation dosimetry was estimated. Tumor sections were stained for CD38 expression. SPRi showed that PF381 had a high affinity for CD38 with a KD of 2.49 × 10^-8 M. HPLC measured a radiolabeling efficiency of 78.45 ± 7.91% for [⁶⁸Ga]Ga-DOTA-PF381, with >98% radiochemical purity. PET imaging revealed rapid and persistent accumulation of radioactivity in CD38-positive H929 tumors, contrasting with negligible uptake in CD38-negative U266 tumors. Biodistribution confirmed higher uptake in H929 tumors (0.75 ± 0.03%ID/g) vs U266 (0.26 ± 0.08%ID/g, <i>P</i> < 0.001). The kidney received the highest radiation dose (3.57 × 10^-02 mSv/MBq), with an effective dose of 1.41 × 10^-02 mSv/MBq. Immunofluorescence imaging supported PET and biodistribution findings. We developed a novel peptide targeting CD38 and proved that ⁶⁸Ga-labeled PF381 had rapid targeting and good tumor penetration capabilities. Therefore, ⁶⁸Ga-labeled PF381 could achieve high sensitivity in vivo imaging for CD38-positive hematological malignancies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1985-1996"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612606","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":"^99mTc-Labeled D-Type PTP as a Plectin-Targeting Single-Photon Emission Computed Tomography Probe for Hepatocellular Carcinoma Imaging.","authors":"JiaLi Gong, Meilin Zhu, Lingzhou Zhao, Taisong Wang, Wenli Qiao, Qingqing Huang, Yan Xing, Jinhua Zhao","doi":"10.1021/acs.bioconjchem.4c00492","DOIUrl":"10.1021/acs.bioconjchem.4c00492","url":null,"abstract":"<p><p>Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide (^DPTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The ^DPTP targeting ability was evaluated <i>in vitro</i> using flow cytometry and <i>ex vivo</i> fluorescence imaging. ^99mTc radiolabeling was performed using tricine and ethylenediamine-<i>N</i>,<i>N</i>'-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of ^DPTP. The radiochemical purity (RCP), <i>in vitro</i> stability, and binding affinity of the prepared ^99mTc-HYNIC-^DPTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of ^99mTc-HYNIC-^DPTP were investigated and compared with those of ^99mTc-labeled L-type PTP (^99mTc-HYNIC-PTP) in HCC tumor-bearing mice. ^DPTP could be efficiently radiolabeled with ^99mTc using the HYNIC/tricine/EDDA system with a high RCP and good <i>in vitro</i> stability. Compared with the L-type PTP, ^DPTP exhibited improved targeting ability, and ^99mTc-HYNIC-^DPTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution <i>in vivo</i>. ^99mTc-HYNIC-^DPTP has great potential as a novel SPECT probe for diagnosing HCC.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1997-2005"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685400","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":"Iron Oxide Nanoparticles Induce Macrophage Secretion of ATP and HMGB1 to Enhance Irradiation-Led Immunogenic Cell Death","authors":"Shuyue Zhan,&nbsp;Zhengwei Cao,&nbsp;Jianwen Li,&nbsp;Fanghui Chen,&nbsp;Xinning Lai,&nbsp;Wei Yang,&nbsp;Yong Teng,&nbsp;Zibo Li,&nbsp;Weizhong Zhang* and Jin Xie*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0048810.1021/acs.bioconjchem.4c00488","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00488https://doi.org/10.1021/acs.bioconjchem.4c00488","url":null,"abstract":"<p >ATP (adenosine triphosphate) and HMGB1 (high mobility group box 1 protein) are key players in treatments that induce immunogenic cell death (ICD). However, conventional therapies, including radiotherapy, are often insufficient to induce ICD. In this study, we explore a strategy using nanoparticle-loaded macrophages as a source of ATP and HMGB1 to complement radiation-induced intrinsic and adaptive immune responses. To this end, we tested three inorganic particles, namely, iron oxide nanoparticles (ION), aluminum oxide nanoparticles (AON), and zinc oxide nanoparticles (ZON), <i>in vitro</i> with bone marrow-derived dendritic cells (BMDCs) and then <i>in vivo</i> in syngeneic tumor models. Our results showed that ION was the most effective of the three nanoparticles in promoting the secretion of ATP and HMGB1 from macrophages without negatively affecting macrophage survival. Secretions from ION-loaded macrophages can activate BMDCs. Intratumoral injection of ION-loaded macrophages significantly enhanced tumor infiltration and activation of dendritic cells and cytotoxic T cells. Moreover, exogenous ION macrophages can enhance the efficacy of radiotherapy. In addition, direct injection of ION can also enhance the efficacy of radiotherapy, which is attributed to ION uptake by and stimulation of endogenous macrophages. Instead of directly targeting cancer cells, our strategy targets macrophages and uses them as a secretory source of ATP and HMGB1 to enhance radiation-induced ICD. Our research introduces a new nanoparticle-based immunomodulatory approach that may have applications in radiotherapy and beyond.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 1","pages":"80–91 80–91"},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084871","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}

{"title":"Wnt-Regulated Therapeutics for Blood-Brain Barrier Modulation and Cancer Therapy.","authors":"Pei An, Yang Tong, Rui Mu, Liang Han","doi":"10.1021/acs.bioconjchem.4c00537","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00537","url":null,"abstract":"<p><p>The Wnt signaling pathway has a significant regulatory part in tissue development and homeostasis. Dysregulation of the Wnt signaling pathway has been associated with many diseases including cancers and various brain diseases, making this signaling pathway a promising therapeutic target for these diseases. In this review, we describe the roles of the Wnt signaling pathway in the blood-brain barrier (BBB) in intracranial tumors and peripheral tumors, from preclinical and clinical perspectives, introduce Wnt-regulated therapeutics including various types of drugs and nanomedicines as BBB modulators for brain-oriented drug delivery and as therapeutic drugs for cancer treatments, and finally discuss limitations and future perspectives for Wnt-regulated therapeutics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833208","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":"Molecular Imaging of Tumor-Infiltrating Lymphocytes in Living Animals Using a Novel mCD3 Fibronectin Scaffold","authors":"Char Wynter,&nbsp;Arutselvan Natarajan*,&nbsp;Clyde John,&nbsp;Kaahini Jain and Ramasamy Paulmurugan*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0050110.1021/acs.bioconjchem.4c00501","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00501https://doi.org/10.1021/acs.bioconjchem.4c00501","url":null,"abstract":"&lt;p &gt;The interaction between cancer cells and immune cells in the tumor microenvironment (TME) plays a crucial role in determining tumor growth, metastasis, and response to treatment. Tumor-infiltrating lymphocytes (TILs) in TME could be a predictive marker for treatment response in various therapeutic interventions, including chemotherapy and immunotherapy. Thus, imaging the tumor immune microenvironment is important for selecting the optimal treatment strategies in cancer therapy. The CD3 protein represents a promising target for diagnostic imaging of TILs &lt;i&gt;in vivo&lt;/i&gt; to assess the immune state of the TME. Although many anti-CD3 antibodies have been explored for this application, the nonspecific immune activation by these antibodies limits their applications. To overcome this issue, we engineered a novel fibronectin III domain (FN3) protein binder (mCD3-FN3;11.8 kDa) against mouse CD3 antigen protein using a yeast display library to image TILs homing &lt;i&gt;in vivo&lt;/i&gt; into the TME. We performed &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; assays to test the mCD3-FN3 binder purity as well as &lt;i&gt;in vivo&lt;/i&gt; targetability in mouse models of syngeneic tumors. We used near-infrared 800 dye conjugated with mCD3-FN3 (IR800-mCD3-FN3) for &lt;i&gt;in vivo&lt;/i&gt; tracking of TILs &lt;i&gt;via&lt;/i&gt; optical imaging. We used three different syngeneic tumors in mice (mCD3&lt;sup&gt;+&lt;/sup&gt; EL4 tumor in C57BL/6 mice, mCD3&lt;sup&gt;–&lt;/sup&gt; CT26 colon tumor, and mCD3&lt;sup&gt;–&lt;/sup&gt; 4T1 breast tumor in BALB/c mice) for imaging TILs &lt;i&gt;in vivo&lt;/i&gt;. C57BL/6 mice bearing EL4 tumors were separated into two groups (blocking [Blk] and nonblocking [Nblk]; &lt;i&gt;n&lt;/i&gt; = 3 per group) and used for &lt;i&gt;in vivo&lt;/i&gt; imaging. Blocking groups received 200 μg of unlabeled mCD3-FN3 2 h prior to the administration of IR800-mCD3-FN3 binder. Each mouse was administered with 25 μg of the IR800-mCD3-FN3 binder and tracked using an IVIS optical imaging system over time. C57BL/6/EL4 mice were imaged at 4 and 24 h post injection of the IR800-mCD3-FN3 binder, and mouse organs were collected at 24 h after final imaging and used for &lt;i&gt;ex vivo&lt;/i&gt; histological imaging. In CT26 and 4T1 tumor models, TILs in TME were imaged 4, 24, and 48 h after binder injection. The NIR imaging of EL4 tumors showed that IR800-mCD3-FN3 can detect both TILs within the tumor and the tumor cells with a high signal-to-background ratio 24 h after initial binder injection with a total radiant efficiency (mean TRE ± SD) of 6.5 × 10&lt;sup&gt;10&lt;/sup&gt; ± 1.5 × 10&lt;sup&gt;10&lt;/sup&gt; [photons/s]/[μW/cm&lt;sup&gt;2&lt;/sup&gt;]. The animals received preinjection of unlabeled mCD3-FN3(Blk) prior to IR800-mCD3-FN3 binder administration and showed a significant level of fluorescence signal reduction (mean TRE ± SD: 1.6 × 10&lt;sup&gt;10&lt;/sup&gt; ± 4.1 × 10&lt;sup&gt;9&lt;/sup&gt;) in the tumor when compared to the EL4-Nblk tumors (&lt;i&gt;p&lt;/i&gt; = 0.006). The mouse group with CT26 and 4T1 tumors where the probe can only bind to TILs within the tumor showed a specific imaging signal (mean TRE ± SD) of 1.1 × 10&lt;sup&gt;11&lt;","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 1","pages":"104–115 104–115"},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084511","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":"FAP-Targeted Fluorescent Imaging Agents to Study Cancer-Associated Fibroblasts In Vivo","authors":"Riley J. Deutsch-Williams,&nbsp;Kelton A. Schleyer,&nbsp;Riddha Das,&nbsp;Jasmine E. Carrothers,&nbsp;Rainer H. Kohler,&nbsp;Claudio Vinegoni and Ralph Weissleder*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0042610.1021/acs.bioconjchem.4c00426","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00426https://doi.org/10.1021/acs.bioconjchem.4c00426","url":null,"abstract":"<p >Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein alpha (FAP) are abundant in tumor microenvironments and represent an emerging target for PET cancer imaging. While different quinolone-based small molecule agents have been developed for whole-body imaging, there is a scarcity of well-validated fluorescent small molecule imaging agents to better study these cells in vivo. Here, we report the synthesis and characterization of a series of fluorescent FAP imaging agents based on the common quinolone azide inhibitor. Our data show excellent performance of some synthesized FAP Targeting Fluorescent probes (FTFs) for both topical application and intravenous delivery to label CAF populations in solid tumors. These results suggest that FTF can be used to study CAF biology and therapeutic targeting in vivo.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 1","pages":"44–53 44–53"},"PeriodicalIF":4.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084399","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}

{"title":"Pathologic Tissue Injury and Inflammation in Mice Immunized with Plasmid DNA-Encapsulated DOTAP-Based Lipid Nanoparticles","authors":"Shasha Peng,&nbsp;Yifan Zhang,&nbsp;Xin Zhao,&nbsp;Yibin Wang,&nbsp;Zihan Zhang,&nbsp;Xin Zhang,&nbsp;Jiali Li,&nbsp;Huiwen Zheng,&nbsp;Ying Zhang,&nbsp;Haijing Shi,&nbsp;Heng Li* and Longding Liu*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0053610.1021/acs.bioconjchem.4c00536","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00536https://doi.org/10.1021/acs.bioconjchem.4c00536","url":null,"abstract":"<p >Ionizable cationic lipids have been developed to mitigate the toxicity of quaternary ammonium lipids, such as DOTAP. Despite its toxicity, DOTAP can promote localization of lipid nanoparticles (LNPs) in target tissues, serving as one of the ionizable cationic helper lipids. Notably, DOTAP-based nanoadjuvants prepared via microfluidic methods showed a better T-cell response. Previous studies showed that DOTAP-based LNPs prepared by the lipid-film method resulted in obvious adverse events. Therefore, our research focused on evaluating the tissue localization and adverse toxicity of a DOTAP-based delivery system prepared through microfluidic techniques. We assessed the delivery efficacy, biodistribution, inflammatory response, and pathological injury in various tissues. In our study, the plasmid DNA encoding the receptor-binding domain (RBD) of SARS-CoV-2 was encapsulated using a mixture of lipids that included DOTAP, DOPE, cholesterol, and DMG-PEG2000 via microfluidic mixing. The LNP-RBDs were smaller than those prepared via the traditional lipid membrane system. We found that LNP-DNA complexes can be effectively delivered and expressed in muscle tissue, with specific antibodies in serum induced postimmunization. Initial distribution of the liposomes was observed in the muscle and liver. Interestingly, both LNPs and DNA showed sustained presence in the lungs and spleen in the group immunized with DNA-encapsulated DOTAP-based LNPs, whereas lower amounts of DNA were detected in the group immunized with dissociative DNA. We detected obvious inflammatory responses and pathological injuries in the muscle, heart, and liver, and the side effects decreased when the immunization dose decreased. These findings suggest that DOTAP-based LNPs have obvious advantages for targeting the lungs and spleen. Additionally, inflammatory responses and pathological injuries occur in a dose-dependent manner in the muscles, heart, and liver. In conclusion, these findings contribute to the development of an LNP delivery system with DOTAP, highlighting its potential to enhance tissue localization and promote high levels of expression when coordinated with ionizable lipids.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"35 12","pages":"2015–2026 2015–2026"},"PeriodicalIF":4.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842124","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":"Gallic Acid-Encapsulated PAMAM Dendrimers as an Antioxidant Delivery System for Controlled Release and Reduced Cytotoxicity against ARPE-19 Cells","authors":"Aorada Sripunya,&nbsp;Chuda Chittasupho,&nbsp;Supachoke Mangmool,&nbsp;Alexander Angerhofer and Witcha Imaram*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0047510.1021/acs.bioconjchem.4c00475","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00475https://doi.org/10.1021/acs.bioconjchem.4c00475","url":null,"abstract":"<p >Poly(amidoamine) (PAMAM) dendrimers have gained significant attention in various research fields, particularly in medicinal compound delivery. Their versatility lies in their ability to conjugate with functional molecules on their surfaces and encapsulate small molecules, making them suitable for diverse applications. Gallic acid is a potent antioxidant compound that has garnered considerable interest in recent years. Our research aims to investigate if the gallic acid-encapsulated PAMAM dendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance radical scavenging, which could potentially slow down the progression of age-related macular degeneration (AMD). Encapsulation of gallic acid in PAMAM dendrimers is a feasible alternative to prevent its degradation and toxicity. <i>In vitro</i> investigation of antioxidant activity was carried out using the DPPH and ABTS radical scavenging assays, as well as the FRAP assay. The IC₅₀ values for DPPH and ABTS assays were determined through nonlinear dose–response curves, correlating the inhibition percentage with the concentration (μg/mL) of the sample and the concentration (μM) of gallic acid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant antioxidant activities as determined by the DPPH, ABTS, and FRAP assays. Moreover, gallic acid-encapsulated PAMAM dendrimers inhibit H₂O₂-induced reactive oxygen species (ROS) production in the human retinal pigment epithelium ARPE-19 cells, thereby improving antioxidant characteristics and potentially retarding AMD progression caused by ROS. In an evaluation of cell viability of ARPE-19 cells using the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects on ARPE-19 cells.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"35 12","pages":"1959–1969 1959–1969"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842450","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}

{"title":"Renally Excretable Molybdenum Disulfide Nanoparticles as Contrast Agents for Dual-Energy Mammography and Computed Tomography","authors":"Lenitza M. Nieves,&nbsp;Emily K. Berkow,&nbsp;Katherine J. Mossburg,&nbsp;Nathaniel H. O,&nbsp;Kristen C. Lau,&nbsp;Derick N. Rosario,&nbsp;Priyash Singh,&nbsp;Xingjian Zhong,&nbsp;Andrew D. A. Maidment and David P. Cormode*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0050810.1021/acs.bioconjchem.4c00508","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00508https://doi.org/10.1021/acs.bioconjchem.4c00508","url":null,"abstract":"<p >Compared with conventional mammography, contrast-enhanced dual-energy mammography (DEM) can improve tumor detection for people with dense breasts. However, currently available iodine-based contrast agents have several drawbacks such as their contraindication for use with renal insufficiency, high-dose requirement, and suboptimal contrast production. Molybdenum disulfide nanoparticles (MoS₂ NPs) have been shown to attenuate X-rays due to molybdenum’s relatively high atomic number while having good biocompatibility. However, work exploring their use as X-ray contrast agents has been limited. In this study, we have developed a novel aqueous synthesis yielding ultrasmall, 2 nm MoS₂ NPs with various small molecule coatings, including glutathione (GSH), penicillamine, and 2-mercaptopropionic acid (2MPA). These nanoparticles were shown to have low in vitro cytotoxicity when tested with various cell lines at concentrations up to 1 mg/mL. For the first time, these particles were shown to generate clinically relevant contrast in DEM. In DEM, MoS₂ NPs generated higher contrast than iopamidol, a commercially available X-ray contrast agent, while also generating substantial contrast in CT. Moreover, MoS₂ NPs demonstrated rapid elimination in vivo, mitigating long-term toxicity concerns. Together, the results presented here suggest the potential utility of MoS₂ NPs as a dual-modality X-ray contrast agent for DEM and CT.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"35 12","pages":"2006–2014 2006–2014"},"PeriodicalIF":4.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842575","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}