Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.
{"title":"GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration.","authors":"Jiale Jin, Xiaowei Xia, Chengxin Ruan, Zhiyuan Luo, Yiqi Yang, Dongyu Wang, Yifang Qin, Dongdong Li, Yong Zhang, Yihe Hu, Pengfei Lei","doi":"10.1186/s12951-024-02787-9","DOIUrl":"https://doi.org/10.1186/s12951-024-02787-9","url":null,"abstract":"<p><p>Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108239","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}
Deoxyribonucleotide (DNA) is uniquely programmable and biocompatible, and exhibits unique appeal as a biomaterial as it can be precisely designed and programmed to construct arbitrary shapes. DNA hydrogels are polymer networks comprising cross-linked DNA strands. As DNA hydrogels present programmability, biocompatibility, and stimulus responsiveness, they are extensively explored in the field of biomedicine. In this study, we provide an overview of recent advancements in DNA hydrogel technology. We outline the different design philosophies and methods of DNA hydrogel preparation, discuss its special physicochemical characteristics, and highlight the various uses of DNA hydrogels in biomedical domains, such as drug delivery, biosensing, tissue engineering, and cell culture. Finally, we discuss the current difficulties facing DNA hydrogels and their potential future development.
脱氧核苷酸(DNA)具有独特的可编程性和生物相容性,可被精确设计和编程以构建任意形状,因此作为生物材料具有独特的吸引力。DNA 水凝胶是由交联 DNA 链组成的聚合物网络。由于 DNA 水凝胶具有可编程性、生物相容性和刺激响应性,因此在生物医学领域得到了广泛的探索。本研究概述了 DNA 水凝胶技术的最新进展。我们概述了 DNA 水凝胶的不同设计理念和制备方法,讨论了其特殊的物理化学特性,并重点介绍了 DNA 水凝胶在生物医学领域的各种用途,如药物输送、生物传感、组织工程和细胞培养。最后,我们讨论了 DNA 水凝胶目前面临的困难及其未来的发展潜力。
{"title":"DNA hydrogels and their derivatives in biomedical engineering applications.","authors":"Rui Wu, Wenting Li, Pu Yang, Naisi Shen, Anqi Yang, Xiangjun Liu, Yikun Ju, Lanjie Lei, Bairong Fang","doi":"10.1186/s12951-024-02791-z","DOIUrl":"https://doi.org/10.1186/s12951-024-02791-z","url":null,"abstract":"<p><p>Deoxyribonucleotide (DNA) is uniquely programmable and biocompatible, and exhibits unique appeal as a biomaterial as it can be precisely designed and programmed to construct arbitrary shapes. DNA hydrogels are polymer networks comprising cross-linked DNA strands. As DNA hydrogels present programmability, biocompatibility, and stimulus responsiveness, they are extensively explored in the field of biomedicine. In this study, we provide an overview of recent advancements in DNA hydrogel technology. We outline the different design philosophies and methods of DNA hydrogel preparation, discuss its special physicochemical characteristics, and highlight the various uses of DNA hydrogels in biomedical domains, such as drug delivery, biosensing, tissue engineering, and cell culture. Finally, we discuss the current difficulties facing DNA hydrogels and their potential future development.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108237","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}
Pub Date : 2024-08-29DOI: 10.1186/s12951-024-02760-6
Yao Fei, Danping Cao, Yanna Li, Zhixiong Wang, Runyu Dong, Menglin Zhu, Peng Gao, Xiaoming Wang, Juan Cai, Xueliang Zuo
Introduction: Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies.
Methods: High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC.
Results: We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance.
Conclusion: Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.
{"title":"Circ_0008315 promotes tumorigenesis and cisplatin resistance and acts as a nanotherapeutic target in gastric cancer.","authors":"Yao Fei, Danping Cao, Yanna Li, Zhixiong Wang, Runyu Dong, Menglin Zhu, Peng Gao, Xiaoming Wang, Juan Cai, Xueliang Zuo","doi":"10.1186/s12951-024-02760-6","DOIUrl":"https://doi.org/10.1186/s12951-024-02760-6","url":null,"abstract":"<p><strong>Introduction: </strong>Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies.</p><p><strong>Methods: </strong>High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC.</p><p><strong>Results: </strong>We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance.</p><p><strong>Conclusion: </strong>Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108236","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}
Pub Date : 2024-08-29DOI: 10.1186/s12951-024-02769-x
Wanheng Zhang, Yan Hou, Shiyi Yin, Qi Miao, Kyubae Lee, Xiaojian Zhou, Yongtao Wang
{"title":"Correction: Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair.","authors":"Wanheng Zhang, Yan Hou, Shiyi Yin, Qi Miao, Kyubae Lee, Xiaojian Zhou, Yongtao Wang","doi":"10.1186/s12951-024-02769-x","DOIUrl":"10.1186/s12951-024-02769-x","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093527","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}
Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS2) as a versatile platform in biomedical applications, few review articles have focused on MoS2-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS2 cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS2 in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS2 in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS2 as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications.
{"title":"Recent developments in two-dimensional molybdenum disulfide-based multimodal cancer theranostics.","authors":"Xinbo Yu, Chen Xu, Jingxu Sun, Hainan Xu, Hanwei Huang, Ziyang Gan, Antony George, Sihui Ouyang, Funan Liu","doi":"10.1186/s12951-024-02785-x","DOIUrl":"10.1186/s12951-024-02785-x","url":null,"abstract":"<p><p>Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS<sub>2</sub>) as a versatile platform in biomedical applications, few review articles have focused on MoS<sub>2</sub>-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS<sub>2</sub> cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS<sub>2</sub> in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS<sub>2</sub> in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS<sub>2</sub> as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093528","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}
Pub Date : 2024-08-27DOI: 10.1186/s12951-024-02779-9
Bin Zeng, Ying Li, Nawaz Khan, Aiyuan Su, Yicheng Yang, Peng Mi, Bin Jiang, Yujie Liang, Li Duan
The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found in all aspects of life. This concept can be quite fitting in the context of extracellular vehicles (EVs) and inflammatory diseases. Over the past decades, numerous studies have revealed that EVs can exhibit dual sides, acting as both pro- and anti-inflammatory agents, akin to the concept of Yin-Yang theory (i.e., two sides of a coin). This has enabled EVs to serve as potential indicators of pathogenesis or be manipulated for therapeutic purposes by influencing immune and inflammatory pathways. This review delves into the recent advances in understanding the Yin-Yang sides of EVs and their regulation in specific inflammatory diseases. We shed light on the current prospects of engineering EVs for treating inflammatory conditions. The Yin-Yang principle of EVs bestows upon them great potential as, therapeutic, and preventive agents for inflammatory diseases.
{"title":"Yin-Yang: two sides of extracellular vesicles in inflammatory diseases.","authors":"Bin Zeng, Ying Li, Nawaz Khan, Aiyuan Su, Yicheng Yang, Peng Mi, Bin Jiang, Yujie Liang, Li Duan","doi":"10.1186/s12951-024-02779-9","DOIUrl":"10.1186/s12951-024-02779-9","url":null,"abstract":"<p><p>The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found in all aspects of life. This concept can be quite fitting in the context of extracellular vehicles (EVs) and inflammatory diseases. Over the past decades, numerous studies have revealed that EVs can exhibit dual sides, acting as both pro- and anti-inflammatory agents, akin to the concept of Yin-Yang theory (i.e., two sides of a coin). This has enabled EVs to serve as potential indicators of pathogenesis or be manipulated for therapeutic purposes by influencing immune and inflammatory pathways. This review delves into the recent advances in understanding the Yin-Yang sides of EVs and their regulation in specific inflammatory diseases. We shed light on the current prospects of engineering EVs for treating inflammatory conditions. The Yin-Yang principle of EVs bestows upon them great potential as, therapeutic, and preventive agents for inflammatory diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080600","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}
Background: Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability.
Results: In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora.
Conclusion: Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis.
{"title":"Natural medicines-derived carbon dots as novel oral antioxidant administration strategy for ulcerative colitis therapy.","authors":"Tong Wu, Xue Bai, Yue Zhang, Ertong Dai, Jinyu Ma, Cai Yu, Chenxin He, Qiannan Li, Yingxin Yang, Hui Kong, Huihua Qu, Yan Zhao","doi":"10.1186/s12951-024-02702-2","DOIUrl":"10.1186/s12951-024-02702-2","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic intestinal inflammation, resulting in a global healthcare challenge with no real specific medicine. Natural medicines are recognized as a potential clinical alternative therapy, but their applications are limited by poor solubility and low bioavailability.</p><p><strong>Results: </strong>In this work, inspired by the natural medicines of ancient China, novel functional carbon dots derived from Magnetite and Medicated Leaven (MML-CDs) were synthesized by hydrothermal method, and confirmed their ultrasmall nano-size (3.2 ± 0.6 nm) and Fe doped surface structure, thereby with excellent gastrointestinal stability, remarkable capabilities in eliminating ROS, and highly biocompatibility. With no external stimuli, the oral administration of MML-CDs demonstrated obvious alleviation to UC. Further experiments pointed that MML-CDs could improve hemostasis capability, suppress inflammation reactions and oxidative stress, and up-regulate the expression of tight junction proteins. Furthermore, MML-CDs also showed well regulation in the dysbiosis of intestinal flora.</p><p><strong>Conclusion: </strong>Overall, above evidence reveals that green-synthesized MML-CDs can significantly alleviate intestinal bleeding, inhibit colon inflammation, and repair colonic barrier damage, further regulating intestinal flora and intestinal inflammation microenvironment. Our findings provide an efficient oral administration of MML-CDs as a novel therapy strategy for ulcerative colitis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073047","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}
Pub Date : 2024-08-27DOI: 10.1186/s12951-024-02767-z
Yu Li, Xiaofan Zhao, Jiaqi Tang, Mengran Yi, Xiaodong Zai, Jun Zhang, Gong Cheng, Yilong Yang, Junjie Xu
The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules.
{"title":"Endogenous capsid-forming protein ARC for self-assembling nanoparticle vaccines.","authors":"Yu Li, Xiaofan Zhao, Jiaqi Tang, Mengran Yi, Xiaodong Zai, Jun Zhang, Gong Cheng, Yilong Yang, Junjie Xu","doi":"10.1186/s12951-024-02767-z","DOIUrl":"10.1186/s12951-024-02767-z","url":null,"abstract":"<p><p>The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080598","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}
Pub Date : 2024-08-27DOI: 10.1186/s12951-024-02765-1
Lei Yang, Wenzhao Li, Yuanjin Zhao, Yongxiang Wang, Luoran Shang
With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.
{"title":"Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment.","authors":"Lei Yang, Wenzhao Li, Yuanjin Zhao, Yongxiang Wang, Luoran Shang","doi":"10.1186/s12951-024-02765-1","DOIUrl":"10.1186/s12951-024-02765-1","url":null,"abstract":"<p><p>With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080599","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}
Pub Date : 2024-08-24DOI: 10.1186/s12951-024-02786-w
Muhammad Ijaz, Ikram Hasan, Tamoor Hamid Chaudhry, Rui Huang, Lan Zhang, Ziwei Hu, Qingqin Tan, Bing Guo
Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy.
{"title":"Bacterial derivatives mediated drug delivery in cancer therapy: a new generation strategy.","authors":"Muhammad Ijaz, Ikram Hasan, Tamoor Hamid Chaudhry, Rui Huang, Lan Zhang, Ziwei Hu, Qingqin Tan, Bing Guo","doi":"10.1186/s12951-024-02786-w","DOIUrl":"10.1186/s12951-024-02786-w","url":null,"abstract":"<p><p>Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055871","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}