{"title":"A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects.","authors":"Ermei Lu, Kecheng Zhou, Jiansen Miao, Yanlin Zhu, Jiyao Tang, Siting Du, Yanzhen Feng, Linyuan Jiang, Tianyao Jiang, Ting Huang, Ping Li, Xinjun Miao, Qi Han, Jian Xiao","doi":"10.1186/s12951-024-03018-x","DOIUrl":"https://doi.org/10.1186/s12951-024-03018-x","url":null,"abstract":"<p><p>Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration. The LNT M2 inherited the inflammatory factor/chemokine receptors from the living M2 macrophages and thus possessing significant inflammatory neutralizing effect. In addition, the scaffold provides slow, sustained release of PTX, promoting axonal regeneration and suppressing scar formation in SCI rats. The LNT M2-based dual-functional scaffold significantly enhances motor function, reduces neuroinflammation, and accelerates axonal regeneration by modulating the inflammatory microenvironment and preventing the formation of glial and fibrotic scars. This approach combines the regenerative effects of low-dose PTX with the immunoregulatory properties of LNT M2, leading to remarkable neurological recovery in SCI rats. Moreover, the scaffold's straightforward preparation, ease of standardization, and \"ready-to-use\" nature make it a promising candidate for acute SCI intervention and future clinical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"8"},"PeriodicalIF":10.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolomics combined with physiology and transcriptomics reveal the regulation of key nitrogen metabolic pathways in alfalfa by foliar spraying with nano-selenium.","authors":"Pengbo Sun, Gentu Ge, Lin Sun, Jian Bao, Muqier Zhao, Junfeng Hao, Yuhan Zhang, Guoshun Liu, Zhijun Wang, Yushan Jia","doi":"10.1186/s12951-024-03073-4","DOIUrl":"10.1186/s12951-024-03073-4","url":null,"abstract":"<p><p>Selenium promotes plant growth and improves nutritional quality, and the role of nano-selenium in alfalfa in regulating nutritional quality is unknown. In this study, using the <sup>15</sup>N labeling method, it was found that nano-selenium could promote plant nitrogen metabolism and photosynthesis by increasing the light energy capture capacity and the activities of key enzymes of the nitrogen metabolism process, leading to an increase in alfalfa nitrogen accumulation and dry matter content. The transcriptome and metabolome revealed that nano-selenium mainly affected the pathways of 'biosynthesis of amino acids', 'starch and sucrose metabolism', 'pentose and glucuronate interconversions', 'pentose phosphate pathway', and 'flavonoid biosynthesis'. At the early stage of nano-selenium treatment, the nitrogen metabolism, sugar metabolism, and flavonoid metabolism pathways were regulated by modulating the expression of genes such as NR, Nir, GS, GOGAT, E3.1.1.11, adh, CHS, FLS, etc., which increased the amount of L-glutamic, L-histidine, glycerone-P, coniferin, naringenin chalcone, and other beneficial substances, thus promoting the acceleration of nitrogen accumulation by plants. In summary, this study provides a better understanding of the mechanisms by which nano-selenium regulates key nitrogen metabolic pathways in alfalfa.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"7"},"PeriodicalIF":10.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenlin Liu, Dong Fan, Jiahui Sun, Guodong Li, Ruoxin Du, Xiaoshuang Zuo, Kuo Zhang, Wangqian Zhang, Shuning Wang, Xiaojv Li, Mingrui Du, Donghui Wang, Qiang Hao, Yingqi Zhang, Meng Li, Cun Zhang, Yuan Gao
{"title":"Inhibition of METTL14 overcomes CDK4/6 inhibitor resistance driven by METTL14-m6A-E2F1-axis in ERα-positive breast cancer.","authors":"Chenlin Liu, Dong Fan, Jiahui Sun, Guodong Li, Ruoxin Du, Xiaoshuang Zuo, Kuo Zhang, Wangqian Zhang, Shuning Wang, Xiaojv Li, Mingrui Du, Donghui Wang, Qiang Hao, Yingqi Zhang, Meng Li, Cun Zhang, Yuan Gao","doi":"10.1186/s12951-024-03021-2","DOIUrl":"https://doi.org/10.1186/s12951-024-03021-2","url":null,"abstract":"<p><p>CDK4/6i, the first-line drug for treating ERα-positive breast cancer, significantly improves clinical outcomes. However, CDK4/6i resistance often develops and remains a major hurdle, and the underlying mechanisms remain challenging to fully investigate. Here, we used Genome-wide CRISPR/Cas9 library screening combined with single-cell sequencing to screen for molecules mediating CDK4/6i resistance and identified METTL14 as a determinant of CDK4/6i sensitivity. Clinical samples and datasets were analyzed and in vitro and in vivo experiments were performed to confirm the critical function of METTL14 in CDK4/6i resistance. Mechanistically, METTL14 can induce an increase in E2F1 expression in breast cancer cells via an m6A IGF2BP2-dependent mechanism and thus promote CDK4/6i resistance. Furthermore, through a small molecule screen, a novel METTL14 inhibitor named WKYMVM, which can restore sensitivity to CDK4/6i in CDK4/6i-resistant breast cancer cells, was identified. Treatment with folate-conjugated liposomes targeting breast cancer cells that contained both a CDK4/6i and WKYMVM revealed the synergistic effect of METTL14 inhibition with CDK4/6i therapy in a CDK4/6i-resistant PDX model. Together, our findings reveal the mechanism of CDK4/6i resistance and provide a strategy for overcoming CDK4/6i resistance via METTL14 inhibition.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"3"},"PeriodicalIF":10.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Opportunities and challenges of bacterial extracellular vesicles in regenerative medicine.","authors":"Jiming Guo, Zhijie Huang, Qinjing Wang, Min Wang, Yue Ming, Weixing Chen, Yisheng Huang, Zhengming Tang, Mingshu Huang, Hongyu Liu, Bo Jia","doi":"10.1186/s12951-024-02935-1","DOIUrl":"10.1186/s12951-024-02935-1","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are membrane-bound vesicles that are shed or secreted from the cell membrane and enveloped by a lipid bilayer. They possess stability, low immunogenicity, and non-cytotoxicity, exhibiting extensive prospects in regenerative medicine (RM). However, natural EVs pose challenges, such as insufficient targeting capabilities, potential biosafety concerns, and limited acquisition pathways. Although engineered EVs demonstrate excellent therapeutic efficacy, challenges such as low production yield and the complexity of engineering modifications constrain their further clinical applications. Bacteria have advantages such as rapid proliferation, diverse gene editing methods, mature cultivation techniques, and relatively easy preparation of bacterial EVs (BEVs), which can be used to effectively address the challenges currently encountered in the field of EVs. This review provides a description of the biogenesis and pathophysiological functions of BEVs, and strategies for optimizing BEVs preparation to attain efficiency and safety are discussed. An analysis of natural characteristics of BEVs is also conducted to explore how to leverage their advantages or mitigate their limitations, thereby overcoming constraints on the application of BEVs in RM. In summary, engineered BEVs possess characteristics such as high production yield, excellent stability, and high drug-delivering capabilities, laying the foundation for their application in RM.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"4"},"PeriodicalIF":10.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927091","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}
{"title":"Advances in 3D printing combined with tissue engineering for nerve regeneration and repair.","authors":"Weifang Liao, Yuying Shi, Zuguang Li, Xiaoping Yin","doi":"10.1186/s12951-024-03052-9","DOIUrl":"https://doi.org/10.1186/s12951-024-03052-9","url":null,"abstract":"<p><p>The repair of nerve damage has long posed a challenge owing to limited self-repair capacity and the highly differentiated nature of nerves. While new therapeutic and pharmacologic interventions have emerged in neurology, their regenerative efficacy remains limited. Tissue engineering offers a promising avenue for overcoming the limitations of conventional treatments and increasing the outcomes of regenerative repair. By implanting scaffolds into damaged nerve tissue sites, the repair and functional reconstruction of nerve injuries can be significantly facilitated. The integration of three-dimensional (3D) printing technology introduces a novel approach for accurate simulation and scalably fabricating neural tissue structures. Tissue-engineered scaffolds developed through 3D printing technology are expected to be a viable therapeutic option for nerve injuries, with broad applicability and continued development. This review systematically examines recent advances in 3D printing and tissue engineering for nerve regeneration and repair. It details the basic principles and construction strategies of neural tissue engineering and explores the crucial role of 3D printing technology. Additionally, it elucidates specific applications and technical challenges associated with this integrated approach, thereby providing valuable insights into innovative strategies and pragmatic implementation within this field.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"5"},"PeriodicalIF":10.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesoporous Prussian blue nanoparticle neuroconduit for the biological therapy targeting oxidative stress reduction, inflammation inhibition, and nerve regeneration.","authors":"Junyi Zhu, Yijia Zhang, Yinuo Sun, Fangzheng Yu, Yang Lu, Qianqian Hu, Jiali Guo, Haijuan Zhang, Tianling Chen, Feifei Lian, Jian Wang, Xiaokun Li, Jian Xiao","doi":"10.1186/s12951-024-02937-z","DOIUrl":"10.1186/s12951-024-02937-z","url":null,"abstract":"<p><p>The applications of nanomaterials in regenerative medicine encompass a broad spectrum. The functional nanomaterials, such as Prussian blue and its derivative nanoparticles, exhibit potent anti-inflammatory and antioxidant properties. By combining it with the corresponding scaffold carrier, the fusion of nanomaterials and biotherapy can be achieved, thereby providing a potential avenue for clinical treatment. The present study demonstrates the fabrication of a Mesoporous Prussian blue nanoparticles (MPBN) functionalized Inverse Opal Film (IOF) neuroconduit for peripheral nerve repair through reverse replication and freeze-drying techniques. The binding of MPBN to the neuroconduit can effectively decreasing reactive oxygen species and inflammatory factors in the vicinity of the residual nerve, thereby providing protective effects on the damaged nerve. Furthermore, comprehensive behavioral, electrophysiological, and pathological analyses unequivocally substantiate the efficacy of MPBN in increasing nerve structure regeneration and ameliorating denervation-induced myopathy. Moreover, MPBN enhances the antioxidant capacity of Schwann cells by activating the AMPK/SIRT1/PGC-1 pathway. The findings suggest that MPBN, a biocompatible nanoparticle, can safeguard damaged nerves by optimizing the microenvironment surrounding nerve cells and augmenting the antioxidant capacity of nerve cells, thereby facilitating nerve regeneration and repair. This also establishes a theoretical foundation for exploring the integration and clinical translation between nanomaterials and biotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"1"},"PeriodicalIF":10.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915178","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}
Ruofei Lu, Bingyang Zhao, Kaiyuan Huo, Hao Liu, Yang Wang, Xingjie Zan, Siwang Hu
{"title":"Facile universal strategy of presenting multifunctional short peptides for customizing desired surfaces.","authors":"Ruofei Lu, Bingyang Zhao, Kaiyuan Huo, Hao Liu, Yang Wang, Xingjie Zan, Siwang Hu","doi":"10.1186/s12951-024-03041-y","DOIUrl":"10.1186/s12951-024-03041-y","url":null,"abstract":"<p><p>Interfacial properties determine biomaterial performances, such as cell adhesion, signal exchange, and biomineralization, which affect the tissue repair cycle and efficiency of clinical applications. Peptides, as short protein sequences that have defined functionalities, are highly stable and easy to synthesize and have enormous potential to reshape interfacial properties. However, the lack of a universal strategy for presenting peptides on various substrates substantially hinders the application of peptides. In this study, we report a facile and universal strategy for customizing desired interfacial functionalities by a well-known layer-by-layer (LbL) technique through the assembly polyphenols with positively charged short peptide-coupling functional sequences. Polyphenol-peptide interactions were elucidated in detail by assembling polyphenols and peptides possessing different characteristics (charged, uncharged, hydrophobic, and sequence length) in combination with molecular dynamics simulations, and isothermal titration calorimetry further revealed the favorable enthalpy change due to electrostatic interactions is the main driving force for assembling peptides with polyphenols. LbL coatings assembled from polyphenols and positively charged peptides exhibited good substrate generalization, stability, cell proliferation, and antioxidant properties, when prepared as hollow capsules by sacrificing the template, exhibited significant pH and ultrasound stimulation responses, which could be suitable candidates for drug carriers. Most importantly, the LbL assembly strategy of positively charged peptides could be utilized to present various functional molecules (such as arginyl-glycyl-aspartic acid (RGD), a cell adhesion motif; CM15, an antibacterial peptide; and PEG, an antifouling surface) on various substrates for customizing desired surfaces. This study not only provides new insights into the understanding and regulation of interactions between proteins/peptides and polyphenols but also paves the way toward the interfacial functionalization of biomaterials.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"2"},"PeriodicalIF":10.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915131","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}
{"title":"Targeting AURKA with multifunctional nanoparticles in CRPC therapy.","authors":"Bin Deng, Binghu Ke, Qixing Tian, Yukui Gao, Qiliang Zhai, Wenqiang Zhang","doi":"10.1186/s12951-024-03070-7","DOIUrl":"10.1186/s12951-024-03070-7","url":null,"abstract":"<p><p>Castration-resistant prostate cancer (CRPC) presents significant therapeutic challenges due to its aggressive nature and poor prognosis. Targeting Aurora-A kinase (AURKA) has shown promise in cancer treatment. This study investigates the efficacy of ART-T cell membrane-encapsulated AMS@AD (CM-AMS@AD) nanoparticles (NPs) in a photothermal-chemotherapy-immunotherapy combination for CRPC. Bioinformatics analysis of the Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) dataset revealed overexpression of AURKA in PCa, correlating with poor clinical outcomes. Single-cell RNA sequencing data from the GEO database showed a significant reduction in immune cells in CRPC. Experimentally, T cell membrane-biomimetic NPs loaded with the AURKA inhibitor Alisertib and chemotherapy drug DTX were synthesized and characterized by dynamic light scattering and transmission electron microscopy, showing good stability and uniformity (average diameter: 158 nm). In vitro studies demonstrated that these NPs inhibited CRPC cell proliferation, increased the G2/M cell population, and elevated apoptosis, confirmed by γH2AX expression. In vivo, CM-AMS@AD NPs accumulated in tumor tissues, significantly slowed tumor growth, decreased proliferation, increased apoptosis, and improved the immune environment, enhancing dendritic cell (DC) maturation and increasing CD8 + /CD4 + ratios. These findings suggest that CM-AMS@AD NPs offer a promising triple-combination therapy for CRPC, integrating photothermal, chemotherapy, and immunotherapy, with significant potential for future clinical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"803"},"PeriodicalIF":10.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903288","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}
Carlos E Romero-Carmona, Juan I Chávez-Corona, Enrique Lima, Hernán Cortés, David Quintanar-Guerrero, María J Bernad-Bernad, Iván Ramos-Martínez, Sheila I Peña-Corona, Javad Sharifi-Rad, Gerardo Leyva-Gómez
{"title":"Nanoparticle and microparticle-based systems for enhanced oral insulin delivery: A systematic review and meta-analysis.","authors":"Carlos E Romero-Carmona, Juan I Chávez-Corona, Enrique Lima, Hernán Cortés, David Quintanar-Guerrero, María J Bernad-Bernad, Iván Ramos-Martínez, Sheila I Peña-Corona, Javad Sharifi-Rad, Gerardo Leyva-Gómez","doi":"10.1186/s12951-024-03045-8","DOIUrl":"10.1186/s12951-024-03045-8","url":null,"abstract":"<p><p>Diabetes mellitus (DM) prevalence is rising worldwide. Current therapies comprising subcutaneous insulin injections can cause adverse effects such as lipodystrophy, local reactions like redness and swelling, fluid retention, and allergic reactions. Nanoparticle carriers for oral insulin are groundbreaking compared to existing methods because they are non-invasive treatments, showing operational convenience, controlled release profile, and ability to simulate the physiological delivery route into the bloodstream. These systems improve patient adherence and have demonstrated the potential to lower blood glucose levels in DM. We present a systematic review and meta-analysis aimed at compiling relevant data to pave the way for developing innovative nano- and microparticles for the oral delivery of insulin. Our analysis of 85 articles revealed that the diminution of glucose levels is not proportional to the administered insulin dosage, which ranged from 1 to 120 International Units (IU). The meta-analysis data indicated that 25 IU of encapsulated porcine insulin did not produce a statistically significant outcome (p = 0.93). In contrast, a dosage of 30 IU was efficacious in eliciting an optimal hypoglycemic effect compared to excipient controls. Parameters such as a high degree of encapsulation (~ 90%), particle size (200-400 nm), and polydispersity index (0.086-0.3) are all associated with lower blood glucose levels. These parameters were also significant in the linear regression analysis. Among the excipients employed, chitosan emerged as a prevalent excipient in formulations due to its biocompatible and biodegradable properties and its ability to establish stable polymeric matrices. Even though oral insulin administration is a promising therapeutic method, it cannot guarantee preclinical safety and therapeutic efficacy yet in regulating glucose levels in diabetic conditions.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"802"},"PeriodicalIF":10.6,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903253","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}