Bioconjugate Chemistry最新文献

{"title":"Wnt-Regulated Therapeutics for Blood-Brain Barrier Modulation and Cancer Therapy","authors":"Pei An,&nbsp;Yang Tong,&nbsp;Rui Mu and Liang Han*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0053710.1021/acs.bioconjchem.4c00537","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00537https://doi.org/10.1021/acs.bioconjchem.4c00537","url":null,"abstract":"<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":"36 2","pages":"136–145 136–145"},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435837","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}

{"title":"Site-Specific Immobilization Boosts the Performance of a Galectin-1 Biosensor","authors":"Dajana Kolanovic,&nbsp;Rajeev Pasupuleti,&nbsp;Jakob Wallner,&nbsp;Georg Mlynek and Birgit Wiltschi*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0046710.1021/acs.bioconjchem.4c00467","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00467https://doi.org/10.1021/acs.bioconjchem.4c00467","url":null,"abstract":"<p >The analysis of protein-bound glycans has gained significant attention due to their pivotal roles in physiological and pathological processes like cell–cell recognition, immune response, and disease progression. Routine methods for glycan analysis are challenged by the very similar physicochemical properties of their carbohydrate components. As an alternative, lectins, which are proteins that specifically bind to glycans, have been integrated into biosensors for glycan detection. However, the effectiveness of protein-based biosensors depends heavily on the immobilization of proteins on the sensor surface. To enhance the sensitivity and/or selectivity of lectin biosensors, it is crucial to immobilize the lectin in an optimal orientation for ligand binding without compromising its function. Random immobilization methods often result in arbitrary orientation and reduced sensitivity. To address this, we explored a directed immobilization strategy relying on a reactive noncanonical amino acid (ncAA) and bioorthogonal chemistry. In this study, we site-specifically incorporated the reactive noncanonical lysine derivative, N^ε-((2-azidoethoxy)carbonyl)-<span>l</span>-lysine, into a cysteine-less single-chain variant of human galectin-1 (scCSGal-1). The reactive bioorthogonal azide group allowed the directed immobilization of the lectin on a biosensor surface using strain-promoted azide–alkyne cycloaddition. Biolayer interferometry data demonstrated that the controlled, directed attachment of scCSGal-1 to the biosensor surface enhanced the binding sensitivity to glycosylated von Willebrand factor by about 12-fold compared to random immobilization. These findings emphasize the importance of controlled protein orientation in biosensor design. They also highlight the power of single site-specific genetic encoding of reactive ncAAs and bioorthogonal chemistry to improve the performance of lectin-based diagnostic tools.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"35 12","pages":"1944–1958 1944–1958"},"PeriodicalIF":4.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.4c00467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842228","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":"Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted 177Lu-Labeled Cancer Theranostics","authors":"Tim Rheinfrank,&nbsp;Viktor Lebruška,&nbsp;Stefan Stangl,&nbsp;Margareta Vojtíčková,&nbsp;Nghia Trong Nguyen,&nbsp;Lena Koller,&nbsp;Jakub Šimeček,&nbsp;Vojtěch Kubíček,&nbsp;Susanne Kossatz* and Johannes Notni*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0048110.1021/acs.bioconjchem.4c00481","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00481https://doi.org/10.1021/acs.bioconjchem.4c00481","url":null,"abstract":"<p >The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne–azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp(<i>N</i>Me)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer’s tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, <i>para</i>-aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"35 12","pages":"1970–1984 1970–1984"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850924","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,&nbsp;Meilin Zhu,&nbsp;Lingzhou Zhao,&nbsp;Taisong Wang,&nbsp;Wenli Qiao,&nbsp;Qingqing Huang*,&nbsp;Yan Xing* and Jinhua Zhao*,&nbsp;","doi":"10.1021/acs.bioconjchem.4c0049210.1021/acs.bioconjchem.4c00492","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00492https://doi.org/10.1021/acs.bioconjchem.4c00492","url":null,"abstract":"<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":"35 12","pages":"1997–2005 1997–2005"},"PeriodicalIF":4.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843301","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":"Comprehensive Review on Bubbles: Synthesis, Modification, Characterization and Biomedical Applications.","authors":"Donald A Fernandes","doi":"10.1021/acs.bioconjchem.4c00137","DOIUrl":"10.1021/acs.bioconjchem.4c00137","url":null,"abstract":"<p><p>Accurate detection, treatment, and imaging of diseases are important for effective treatment outcomes in patients. In this regard, bubbles have gained much attention, due to their versatility. Bubbles usually 1 nm to 10 μm in size can be produced and loaded with a variety of lipids, polymers, proteins, and therapeutic and imaging agents. This review details the different production and loading methods for bubbles, for imaging and treatment of diseases/conditions such as cancer, tumor angiogenesis, thrombosis, and inflammation. Bubbles can also be used for perfusion measurements, important for diagnostic and therapeutic decision making in cardiac disease. The different factors important in the stability of bubbles and the different techniques for characterizing their physical and chemical properties are explained, for developing bubbles with advanced therapeutic and imaging features. Hence, the review provides important insights for researchers studying bubbles for biomedical applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":" ","pages":"1639-1686"},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386377","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}