Journal of Nanobiotechnology最新文献

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Supramolecular nanotherapeutics based on cucurbiturils.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-23 DOI: 10.1186/s12951-024-03024-z
Maiyier Muheyati, Guangheng Wu, Yilin Li, Ziting Pan, Yueyue Chen
{"title":"Supramolecular nanotherapeutics based on cucurbiturils.","authors":"Maiyier Muheyati, Guangheng Wu, Yilin Li, Ziting Pan, Yueyue Chen","doi":"10.1186/s12951-024-03024-z","DOIUrl":"10.1186/s12951-024-03024-z","url":null,"abstract":"<p><p>Polymeric biomaterials have important applications in aiding clinical disease treatment, including drug delivery, bioimaging, and tissue engineering. Currently, conventional tumor chemotherapy faces obstacles such as poor solubility/stability, inability to target, and uncontrolled drug release in clinical trials, for which the emergence of supramolecular material therapeutics combining non-covalent interactions with conventional therapies is a very promising candidate. Due to their molecular recognition abilities with a range of biomolecules, cucurbit[n]uril (CB[n]), a type of macrocyclic receptors with robust backbones, hydrophobic cavities, and carbonyl-binding channels, have garnered a lot of attention. Therefore, this paper reviews recent advances in CB[n] material-based supramolecular therapeutics for clinical treatments, including targeted delivery applications and related imaging and sensing systems. This study also covers the distinctive benefits of CB materials for biological applications, as well as the trends and prospects of this interdisciplinary subject, based on numerous state-of-the-art research findings.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"790"},"PeriodicalIF":10.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A shielded cascade of targeted nanocarriers spanning multiple microenvironmental barriers for inflammatory disease therapy.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-23 DOI: 10.1186/s12951-024-03075-2
Fengyi Liu, Xu Wang, Mingxing Ren, Ping He, Yuzhou Li, Jing Cui, Sheng Yang
{"title":"A shielded cascade of targeted nanocarriers spanning multiple microenvironmental barriers for inflammatory disease therapy.","authors":"Fengyi Liu, Xu Wang, Mingxing Ren, Ping He, Yuzhou Li, Jing Cui, Sheng Yang","doi":"10.1186/s12951-024-03075-2","DOIUrl":"10.1186/s12951-024-03075-2","url":null,"abstract":"<p><strong>Background: </strong>The multi-biological barriers present in the inflammatory microenvironment severely limit the targeted aggregation of anti-inflammatory drugs in the lesion area. However, conventional responsive drug carriers inevitably come into contact with several pro-responsive stimulatory mediators simultaneously, leading to premature drug release and loss of most therapeutic effects. Breaking through the multi-level barriers of the inflammatory microenvironment is essential to improve the enrichment and bioavailability of drugs.</p><p><strong>Results: </strong>In this study, we propose a novel two-stage structural strategy to build shielded cascades of targeted nanocarriers (FA-PTP@Que) through inflammatory mediators, using cascade structures to cross multiple environmental barriers. The cascade structure of FA-PTP@Que is responsive to inflammatory mediators and exhibits ideal pathological microenvironmental response and drug release properties. FA-PTP@Que has shown good macrophage regulation and anti-inflammatory effects by efficiently targeting macrophages, scavenging intracellular reactive oxygen species (ROS), and down-regulating the secretion of pro-inflammatory factors. Significantly, in mice with arthritis and colitis, FA-PTP@Que enriches and targets macrophages at the sites of arthritis and colitis, showing significant anti-inflammatory effects.</p><p><strong>Conclusion: </strong>FA-PTP@Que combines active chemotaxis of nanocarriers to inflammatory tissues and active targeting of effector cells, acting precisely at each barrier level in different microenvironments by responding to inflammatory mediators and overcoming the multiple barriers in the inflammatory microenvironment. This innovative strategy can effectively break through various inflammatory microenvironments and has the potential application to other inflammatory diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"789"},"PeriodicalIF":10.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Click chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-23 DOI: 10.1186/s12951-024-03071-6
Agustín Robles-Remacho, Ismael Martos-Jamai, Mavys Tabraue-Chávez, Araceli Aguilar-González, Jose A Laz-Ruiz, M Victoria Cano-Cortés, F Javier López-Delgado, Juan J Guardia-Monteagudo, Salvatore Pernagallo, Juan J Diaz-Mochon, Rosario M Sanchez-Martin
{"title":"Click chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells.","authors":"Agustín Robles-Remacho, Ismael Martos-Jamai, Mavys Tabraue-Chávez, Araceli Aguilar-González, Jose A Laz-Ruiz, M Victoria Cano-Cortés, F Javier López-Delgado, Juan J Guardia-Monteagudo, Salvatore Pernagallo, Juan J Diaz-Mochon, Rosario M Sanchez-Martin","doi":"10.1186/s12951-024-03071-6","DOIUrl":"10.1186/s12951-024-03071-6","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI). Given the potential of miR-122 as a biomarker, its effective detection is important for accurate diagnosis. However, miRNA detection methods still face challenges, particularly in terms of accurately identifying miRNA isoforms that may differ by only a single base. Here, with the aim of advancing accessible methods for the detection of miRNAs with single-base specificity, we have developed a robust dual nanosystem that leverages the simplicity of click chemistry reactions. Using the dual nanosystem, we successfully detected miR-122 at single-base resolution using flow cytometry and analysed its expression in various tumour cell lines with high specificity and strong correlation with TaqMan assay results. We also detected miR-122 in serum and identified four single nucleotide variations in its sequence. The chemistry employed in this dual nanosystem is highly versatile and offers a promising opportunity to develop nanoparticle-based strategies that incorporate click chemistry and bioorthogonal chemistry for the detection of miRNAs and their isoforms.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"791"},"PeriodicalIF":10.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel self-assembling peptide nanofiber hydrogel with glucagon-like peptide-1 functionality enhances islet survival to improve islet transplantation outcome in diabetes treatment.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-23 DOI: 10.1186/s12951-024-03072-5
Xiangheng Cai, Mengnan Zhang, Jiaqi Zou, Le Wang, Yixiang Zhan, Dandan Li, Tingsheng Jiang, Nijat Alim, Zhaoce Liu, Jiuxia Yang, Na Liu, Tengli Liu, Peng Sun, Xuejie Ding, Boya Zhang, Zewen Liu, Xuelian Wang, Rui Liang, Jinzhen Cai, Jie Gao, Jinglin Cao, Shusen Wang
{"title":"A novel self-assembling peptide nanofiber hydrogel with glucagon-like peptide-1 functionality enhances islet survival to improve islet transplantation outcome in diabetes treatment.","authors":"Xiangheng Cai, Mengnan Zhang, Jiaqi Zou, Le Wang, Yixiang Zhan, Dandan Li, Tingsheng Jiang, Nijat Alim, Zhaoce Liu, Jiuxia Yang, Na Liu, Tengli Liu, Peng Sun, Xuejie Ding, Boya Zhang, Zewen Liu, Xuelian Wang, Rui Liang, Jinzhen Cai, Jie Gao, Jinglin Cao, Shusen Wang","doi":"10.1186/s12951-024-03072-5","DOIUrl":"10.1186/s12951-024-03072-5","url":null,"abstract":"<p><p>Islet transplantation is a promising therapy for diabetes, yet the limited survival and functionality of transplanted islet grafts hinder optimal outcomes. Glucagon-like peptide-1 (GLP-1), an endogenous hormone, has shown potential to enhance islet survival and function; however, its systemic administration can result in poor localization and undesirable side effects. To address these challenges, we developed a novel peptide-based nanofiber hydrogel incorporating GLP-1 functionality for localized delivery. By conjugating the FFG tripeptide (a self-assembling motif derived from phenylalanine-phenylalanine-glycine) to the C-terminus of native GLP-1, we engineered GLP-1-FFG, a self-assembling peptide that forms a robust nanofiber structure resistant to enzymatic degradation. When GLP-1-FFG co-assembles with the biotin-<sup>D</sup>FYIGSRGD peptide (referred to as SupraGel), a self-assembling supramolecular polypeptide hydrogel we previously identified containing motifs derived from extracellular matrix components, the resulting hydrogel (SupraGel + GLP-1-FFG) creates a stable nanofibrous network with excellent rheological properties. In vitro, this nanofiber hydrogel significantly improves islet function and survival. Bulk RNA sequencing results demonstrate that the hydrogel suppresses the expression of hypoxia-related genes, downregulates pro-inflammatory genes, and upregulates genes associated with islet function. Further analysis reveals that these effects are related to the activation of the AKT signaling pathway. In a syngeneic mouse islet transplantation model, the localized application of SupraGel + GLP-1-FFG at the renal subcapsular islet transplant site significantly enhanced the efficacy of marginal-dose islet transplantation, as shown by improved glycemic control, faster and higher rates of diabetes reversal, better glucose tolerance, and greater islet graft survival in diabetic recipient mice. This innovative nanotechnology-based hydrogel offers a promising strategy for enhancing the efficacy of islet grafts in transplantation therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"792"},"PeriodicalIF":10.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-22 DOI: 10.1186/s12951-024-03065-4
Xueli Jia, Bochuan Yuan, Wanmei Wang, Ke Wang, Dandan Ling, Meng Wei, Yadan Hu, Wanting Guo, Ziyuan Chen, Lina Du, Yiguang Jin
{"title":"Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens.","authors":"Xueli Jia, Bochuan Yuan, Wanmei Wang, Ke Wang, Dandan Ling, Meng Wei, Yadan Hu, Wanting Guo, Ziyuan Chen, Lina Du, Yiguang Jin","doi":"10.1186/s12951-024-03065-4","DOIUrl":"10.1186/s12951-024-03065-4","url":null,"abstract":"<p><p>In the post-COVID-19 era, drug-resistant bacterial infections emerge as one of major death causes, where multidrug-resistant Acinetobacter baumannii (MRAB) and drug-resistant Pseudomonas aeruginosa (DRPA) represent primary pathogens. However, the classical antibiotic strategy currently faces the bottleneck of drug resistance. We develop an antimicrobial strategy that applies the selective delivery of CRISPR/Cas9 plasmids to pathogens with biomimetic cationic hybrid vesicles (BCVs), irrelevant to bacterial drug resistance. CRISPR/Cas9 plasmids were constructed, replicating in MRAB or DRPA and expressing ribonucleic proteins, leading to irreparable chromosomal lesions; however, delivering the negatively charged plasmids with extremely large molecular weight to the pathogens at the infection site became a huge challenge. We found that the BCVs integrating the bacterial out membrane vesicles and cationic lipids efficiently delivered the plasmids in vitro/in vivo to the pathogens followed by effective internalization. The BCVs were used by intratracheal or topical hydrogel application against MRAB pulmonary infection or DRPA wound infection, and both of the two pathogens were eradicated from the lung or the wound. CRISPR/Cas9 plasmid-loaded BCVs become a promising medication for drug-resistant bacteria infections.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"787"},"PeriodicalIF":10.6,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resistant starch grafted cerium-sulfasalazine infinite coordination polymers synergistically remold intestinal metabolic microenvironment for inflammatory bowel disease therapy.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-20 DOI: 10.1186/s12951-024-03043-w
Jing Zhang, Liyuan Zhao, Along Liang, Xueyan Geng, Mengmeng Hou, Haojie Cheng, Shouren Zhang, Baocheng Yang, Junbo Li, Jian Chen
{"title":"Resistant starch grafted cerium-sulfasalazine infinite coordination polymers synergistically remold intestinal metabolic microenvironment for inflammatory bowel disease therapy.","authors":"Jing Zhang, Liyuan Zhao, Along Liang, Xueyan Geng, Mengmeng Hou, Haojie Cheng, Shouren Zhang, Baocheng Yang, Junbo Li, Jian Chen","doi":"10.1186/s12951-024-03043-w","DOIUrl":"10.1186/s12951-024-03043-w","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease which is closely related with the overproduced reactive oxygen species (ROS), increased pro-inflammatory cytokines and disordered intestinal microbes. However, current therapeutic methods usually ignored the interrelation among the pathogenesis, and mainly focused on a single factor, inducing clinical outcomes unsatisfied. Herein, biocompatible infinite coordination polymers of drugs (Ce-SASP-RS ICPs) composed of Ce ions, FDA-approved drug sulfasalazine (SASP) and natural ingredient resistant starch (RS) were developed for synergistic treatment of IBD. The proper Ce<sup>3+</sup>/Ce<sup>4+</sup> ratio in Ce-SASP-RS ICPs can endow them with SOD-like activities, POD-like activities and •OH scavenging ability, which guarantee Ce-SASP-RS ICPs to simultaneously kill bacteria and maintain ROS balance through cascade reactions. Owing to the recovered redox balance microenvironment, SASP in Ce-SASP-RS ICPs can better play their anti-inflammatory function. Moreover, benefitting from the recovered metabolic balance of ROS and inflammatory cytokines in colon, resistant starch can also function better in modifying gut microbiota through generating short-chain fatty acids. Collectively, Ce-SASP-RS ICPs can synergistically restore intestinal metabolic microenvironment through modulating redox balance, attenuating inflammation and modifying intestinal flora. Hence, in view of the mutual influences among IBD pathogenesis, this work presents a synergistic intervention approach for effectively treating IBD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"785"},"PeriodicalIF":10.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted lipid nanoparticles distributed in hydrogel treat osteoarthritis by modulating cholesterol metabolism and promoting endogenous cartilage regeneration.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-20 DOI: 10.1186/s12951-024-02965-9
Zhibo Zhao, Peng Wang, Ziyang Li, Xingchen Wei, Shishuo Li, Xiaoqing Lu, Shimin Dai, Benzhao Huang, Zhentao Man, Wei Li
{"title":"Targeted lipid nanoparticles distributed in hydrogel treat osteoarthritis by modulating cholesterol metabolism and promoting endogenous cartilage regeneration.","authors":"Zhibo Zhao, Peng Wang, Ziyang Li, Xingchen Wei, Shishuo Li, Xiaoqing Lu, Shimin Dai, Benzhao Huang, Zhentao Man, Wei Li","doi":"10.1186/s12951-024-02965-9","DOIUrl":"10.1186/s12951-024-02965-9","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common disease in aging joints and has characteristics of cartilage destruction and inflammation. It is currently considered a metabolic disease, and the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes plays a crucial catabolic regulatory role in its pathogenesis. Targeting of this axis in chondrocytes may provide a therapeutic approach for OA treatment. Here, in this study, we propose to use a combination of stem cell-recruiting hydrogels and lipid nanoparticles (LNPs) that modulate cholesterol metabolism to jointly promote a regenerative microenvironment. Specifically, we first developed an injectable, bioactive hydrogel composed of self-assembling peptide nanofibers that recruits endogenous synovial stem cells (SMSCs) and promotes their chondrogenic differentiation. At the same time, LNPs that regulate cholesterol metabolism are incorporated into the hydrogel and slowly released, thereby improving the inflammatory environment of OA. Enhancements were noted in the inflammatory conditions associated with OA, alongside the successful attraction of mesenchymal stem cells (MSCs) from the synovial membrane. These cells were then observed to differentiate into chondrocytes, contributing to effective cartilage restoration and chondrocyte regeneration, thereby offering a promising approach for OA treatment. In summary, this approach provides a feasible siRNA-based therapeutic option, offering a potential nonsurgical solution for treatment of OA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"786"},"PeriodicalIF":10.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and evaluation of a single domain antibody targeting folate receptor alpha for radioligand therapy.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-19 DOI: 10.1186/s12951-024-03008-z
Jonatan Dewulf, Sam Massa, Laurent Navarro, Yana Dekempeneer, Francis Santens, Hannelore Ceuppens, Karine Breckpot, Jo A Van Ginderachter, Tony Lahoutte, Matthias D'Huyvetter, Nick Devoogdt
{"title":"Development and evaluation of a single domain antibody targeting folate receptor alpha for radioligand therapy.","authors":"Jonatan Dewulf, Sam Massa, Laurent Navarro, Yana Dekempeneer, Francis Santens, Hannelore Ceuppens, Karine Breckpot, Jo A Van Ginderachter, Tony Lahoutte, Matthias D'Huyvetter, Nick Devoogdt","doi":"10.1186/s12951-024-03008-z","DOIUrl":"10.1186/s12951-024-03008-z","url":null,"abstract":"<p><strong>Background: </strong>Folate receptor alpha (FRα) overexpression is seen in many cancers. Radioligand therapy (RLT) has emerged as a promising tool to target FRα and has been investigated previously, but further progression was limited due to high kidney retention and, subsequently, toxicity. To circumvent this, we present here the development of a [<sup>131</sup>I]I-GMIB-conjugated anti-human FRα (hFRα) single-domain antibody (sdAb), with intrinsically fast renal clearance and concomitant low kidney retention. We report the hit-to-lead development of an anti-hFRα sdAb. We evaluated its potential in vitro and assessed its targeting ability using SPECT imaging in hFRα-knockin and tumour-bearing mice. The toxicity and therapeutic efficacy of the [<sup>131</sup>I]I-GMIB-sdAb were investigated in mouse models.</p><p><strong>Results: </strong>The lead anti-hFRα sdAb 2BD42 was developed with picomolar affinities, low k<sub>off</sub>, and radiolabelled using [<sup>131</sup>I]I with yields of > 41% and purity > 99%. [<sup>131</sup>I]I-GMIB-2BD42 retained tumour uptake (> 5%IA/g at 1 h p.i. and > 1.5%IA/g at 24 h p.i.) and fast kidney clearance (< 1%IA/g at 24 h p.i.) in athymic and hFRα-knock-in mice. Athymic mice bearing hFRα-positive xenografts treated with [<sup>131</sup>I]I-GMIB-2BD42 showed prolonged survival without toxicity compared to animals that received the vehicle solution or radioactive control.</p><p><strong>Conclusion: </strong>The therapeutic lead radiopharmaceutical [<sup>131</sup>I]I-GMIB-2BD42 showed fast pharmacokinetics with specific retention in hFRα + tumours. In addition, we report therapeutic efficacy with no signs of toxicity. In this study, we successfully designed a new drug for RLT, overcoming previous limitations, such as high kidney retention, which could aid in revitalising FRα-targeted radiotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"763"},"PeriodicalIF":10.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-19 DOI: 10.1186/s12951-024-03036-9
Haribalan Perumalsamy, Xiao Xiao, Hyoung-Yun Han, Jung-Hwa Oh, Seokjoo Yoon, Min Beom Heo, Tae Geol Lee, Hyun-Yi Kim, Tae-Hyun Yoon
{"title":"Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide.","authors":"Haribalan Perumalsamy, Xiao Xiao, Hyoung-Yun Han, Jung-Hwa Oh, Seokjoo Yoon, Min Beom Heo, Tae Geol Lee, Hyun-Yi Kim, Tae-Hyun Yoon","doi":"10.1186/s12951-024-03036-9","DOIUrl":"10.1186/s12951-024-03036-9","url":null,"abstract":"<p><p>The prospective use of food additive titanium dioxide (E171 TiO<sub>2</sub>) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO<sub>2</sub> can translocate in bloodstream and induce a diverse immunological response by activating the immune system, which can be either pro-inflammatory or immune-suppressive. Nevertheless, their cellular or immunologic responses in a heterogeneous population of the immune system following exposure of food additive E171 TiO<sub>2</sub> is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO<sub>2</sub> (5 mg/kg bw per day) via non-invasive intratracheal instillation for 13 weeks. After the 4 weeks recovery period, 3 mL of blood samples from both treated and untreated groups were collected for scRNAseq analysis. Firstly, granulocyte G1 activated innate immune response through the upregulation of genes involved in pro-inflammatory cytokine mediated cytotoxicity. Whereas NK cells resulted in heterogeneity role depending on the subsets where NK1 significantly inhibited cytotoxicity, whereas NK2 and NK3 subsets activated pro-B cell population & inhibited T cell mediated cytotoxicity respectively. While NKT_1 activated innate inflammatory responses which was confirmed by cytotoxic CD8+ T killer cell suppression. Similarly, NKT_2 cells promote inflammatory response by releasing lytic granules and MHC-I complex inhibition to arrest cytotoxic T killer cell responses. Conversely, NKT_3 suppressed inflammatory response by release of anti-inflammatory cytokines suggesting the functional heterogeneity of NKT subset. The formation of MHC-I or MHC-II complexes with T-cell subsets resulted in neither B and T cell dysfunction nor cytotoxic T killer cell inhibition suppressing adaptive immune response. Overall, our research offers an innovative high-dimensional approach to reveal immunological and transcriptomic responses of each cell types at the single cell level in a complex heterogeneous cellular environment by reassuring a precise assessment of immunological response of E171 TiO<sub>2</sub>.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"765"},"PeriodicalIF":10.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An integrated "Engage & Evasion" approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy.
IF 10.6 1区 生物学
Journal of Nanobiotechnology Pub Date : 2024-12-19 DOI: 10.1186/s12951-024-03032-z
Hongman Liu, Mengting Li, Bing Xiang, Ziying Yang, Shiyu Cao, Wen Gong, Jingjing Li, Wenjing Zhou, Liang Ding, Qingsong Tang, Shengnan Wang, Jin Tang, Zixuan Fan, Ke He, Xuan Jiang, Zhenya Shen, Weiqian Chen, Jie Hui
{"title":"An integrated \"Engage & Evasion\" approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy.","authors":"Hongman Liu, Mengting Li, Bing Xiang, Ziying Yang, Shiyu Cao, Wen Gong, Jingjing Li, Wenjing Zhou, Liang Ding, Qingsong Tang, Shengnan Wang, Jin Tang, Zixuan Fan, Ke He, Xuan Jiang, Zhenya Shen, Weiqian Chen, Jie Hui","doi":"10.1186/s12951-024-03032-z","DOIUrl":"10.1186/s12951-024-03032-z","url":null,"abstract":"<p><p>Ischemic diseases are major contributors to global morbidity and mortality, posing a substantial threat to human health. Extracellular vesicles (EVs) play an essential role in enhancing neovascularization in ischemic tissues, thereby facilitating tissue repair and regeneration. However, the utilization of EVs is hindered by their rapid uptake and clearance by the mononuclear phagocyte system (MPS), which markedly impedes their therapeutic efficacy and organ-specific accumulation. Notably, CD47, upon binding to signal regulatory protein alpha, initiates a \"don't eat me\" signal, enabling immune evasion from the MPS. Our research has demonstrated that phagocytes predominantly engulf CD47<sup>low</sup> dendritic DC2.4 cell-derived EVs (DV), while engineered CD47<sup>high</sup> EVs (MV<sup>47</sup>) experience minimal ingestion. Leveraging these findings, we have developed a dual-faceted \"Engage & Evasion\" strategy. Initially, DVs were employed to saturate the MPS, serving as the \"engage\" component. Subsequently, MV<sup>47</sup>, fortified with CD47, was introduced for \"evasion\" purposes. This approach effectively minimized entrapment by the liver and spleen, boosted serum concentration, and enhanced final accumulation in non-MPS organs. In summary, our \"Engage & Evasion\" therapeutic strategy offers a promising avenue to enhance EV therapeutic potential against ischemic challenges through improved systemic distribution.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"770"},"PeriodicalIF":10.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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