Acta Biomaterialia最新文献

{"title":"Research progress on the performance of expandable systems for long-term gastric retention","authors":"Xin Jin ,&nbsp;Heng Li ,&nbsp;Wei Zhang ,&nbsp;Kairong Qin ,&nbsp;Chengwei Wu","doi":"10.1016/j.actbio.2025.01.002","DOIUrl":"10.1016/j.actbio.2025.01.002","url":null,"abstract":"<div><div>Gastroretentive systems have gained attention due to their prolonged retention time in the human body, and they have the potential to improve treatment effects, simplify treatment regimens, and improve patient compliance. Among these systems, expandable gastroretentive systems (EGRSs) have emerged as an important type of carrier that can reside in the stomach for a desired period through on-demand expansion for drug delivery, obesity intervention, and medical diagnosis. As the physiological environment significantly influences the performance of EGRSs, here, the physiological factors such as the stomach's physiological structure and activity pattern, and the character of gastric juice are summarized. Following this, the research progress of EGRSs from ingestion to removal for long-term gastric retention is discussed with respect to the influencing factors and reinforcement strategies in mechanics. Additionally, as the duration of gastric retention increases, safety concerns arise. As such, safety issues in terms of removal after retention or in an emergency are also analyzed. Finally, the biomedical application of EGRSs as diagnostic and therapeutic tools and the potential direction for further research are discussed.</div></div><div><h3>Statement of significance</h3><div>Expandable gastroretentive systems (EGRSs) resist gastric emptying due to their size exceeding the pylorus diameter, offering promising advantages for obesity intervention, drug delivery, and carrying sensors. However, a long gastroretentive time only by such a size mismatch is hard to be achieved due to the uninterrupted stomach contraction and gastric juice erosion. Recent studies indicate that the retention time and stability of EGRSs can be regulated by adjusting their mechanical properties. Hence, this review summarizes the state-of-art progress of EGRSs for long-term gastric retention from a mechanical perspective for the first time, focuses on material components and synthesis methods, and the reinforcement strategies, and suggests the required mechanical property parameters of EGRSs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 1-19"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIEZO1-mediated mechanotransduction regulates collagen synthesis on nanostructured 2D and 3D models of fibrosis","authors":"Neda Rashidi ,&nbsp;Natalia S. Harasymowicz ,&nbsp;Alireza Savadipour ,&nbsp;Nancy Steward ,&nbsp;Ruhang Tang ,&nbsp;Sara Oswald ,&nbsp;Farshid Guilak","doi":"10.1016/j.actbio.2024.12.034","DOIUrl":"10.1016/j.actbio.2024.12.034","url":null,"abstract":"<div><div>Progressive fibrosis can lead to tissue malfunction and organ failure due to the pathologic accumulation of a collagen-rich extracellular matrix. <em>In vitro</em> models provide useful tools for deconstructing the roles of specific biomechanical or biological mechanisms, such as substrate micro- and nanoscale architecture, in these processes for identifying potential therapeutic targets. Here, we investigated how the mechanosensitive ion channel PIEZO1 influences fibrotic gene and protein expression in adipose-derived stem cells (hASCs). Specifically, we examined the role of PIEZO1 and the mechanosensitive transcription factors YAP/TAZ in sensing aligned or non-aligned substrate architecture to regulate collagen formation. We utilized both 2D microphotopatterned substrates and 3D electrospun polycaprolactone (PCL) substrates to study the role of culture dimensionality. We found that PIEZO1 regulates collagen synthesis in hASCs in a manner that is sensitive to substrate architecture. Activation of PIEZO1 induced significant morphological changes in hASCs, particularly when cultured on aligned substrates, leading to a 30–40 % reduction in cell spreading area and increased cell elongation, in 3D-aligned cultures. Picrosirius Red staining and immunoblotting revealed that PIEZO1 activation reduced collagen accumulation in 3D culture. While YAP translocated to the cytoplasm following PIEZO1 activation, depleting YAP and TAZ did not change collagen expression significantly downstream of PIEZO1 activation, implying that YAP/TAZ translocation from the nucleus and decreased collagen synthesis may be independent consequences of PIEZO1 activation. Our studies demonstrate a role for PIEZO1 in cellular mechanosensing of substrate architecture and provide targetable pathways for treating fibrosis and for enhancing tissue-engineered and regenerative approaches for fibrous tissue repair.</div></div><div><h3>Statement of significance</h3><div>This study examines how cells sense and respond to their physical environment via PIEZO1 mechanotransduction. We discovered that cells use PIEZO1 to detect the alignment of surrounding structures, influencing the production of collagen - a key component in fibrosis. Our study used both 2D and 3D models to mimic different tissue environments, providing new insights into how cellular responses change in more complex settings. Importantly, we found that activating PIEZO1 alters cell shape and collagen production, especially on aligned surfaces. Interestingly, while PIEZO1 activation caused YAP translocation to the cytoplasm, this translocation did not directly affect collagen production. This work advances our understanding of fibrosis development and identifies PIEZO1 as a potential target for new therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 242-254"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyphenol-mediated assembly of toll-like receptor 7/8 agonist nanoparticles for effective tumor immunotherapy","authors":"Yilei Zhao ,&nbsp;Xiaonan Zhao ,&nbsp;Xuechun Wang ,&nbsp;Zilin Ma ,&nbsp;Jie Yan ,&nbsp;Songyan Li ,&nbsp;Ning Wang ,&nbsp;Jianwei Jiao ,&nbsp;Jiwei Cui ,&nbsp;Guiqiang Zhang","doi":"10.1016/j.actbio.2024.12.060","DOIUrl":"10.1016/j.actbio.2024.12.060","url":null,"abstract":"<div><div>Toll-like receptor (TLR) 7/8 agonists have shown significant potential in tumor immunotherapy. However, the limited pharmacokinetic properties and systemic toxicity resulting from off-target effects limits their biomedical applications. We here report the polyphenol-mediated assembly of resiquimod (R848, a TLR7/8 agonist) nanoparticles (RTP NPs) to achieve tumor-selective immunotherapy while avoiding systemic adverse effects. Upon intravenous administration, the prepared RTP NPs are effectively accumulated at tumor sites, which increase their bioavailability and reduce systemic inflammation. RTP NPs can trigger a potent antitumor immune response in a mouse tumor model to inhibit tumor growth. Additionally, after subcutaneous injection at the tail base, RTP NPs efficiently migrate to the lymph nodes, where they elicit immune memory to prevent tumorigenesis. This study underscores the potential application of polyphenol-mediated assembly in developing nanomedicines with reduced toxicity for tumor-specific immunotherapy.</div></div><div><h3>Statement of significance</h3><div>Toll-like receptor agonist (R848) nanoparticles for tumor-selective immunotherapy were synthesized through polyphenol-mediated assembly, a method that simplifies preparation process and minimizes potential side effects. Intravenously administered these nanoparticles effectively extended circulation time, enhanced tumor enrichment, and reduced systemic inflammation, thus augmenting the bioavailability and minimizing the side effects of R848. The nanoparticles significantly inhibited tumor growth by triggering a potent antitumor immune response, including dendritic cell maturation, macrophage polarization, T-cell infiltration, and cytokine secretion. Moreover, after subcutaneous injection at the tail base, they can elicit immune memory to prevent tumorigenesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 417-428"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tumor-targeting porphyrin-micelle with enhanced STING agonist delivery and synergistic photo-/immuno- therapy for cancer treatment","authors":"Yuqing Pan ,&nbsp;Haijing Qu ,&nbsp;Han Chen ,&nbsp;Wei Cheng ,&nbsp;Zhiran Duan ,&nbsp;Jiaojiao Yang ,&nbsp;Ning Wang ,&nbsp;Jie Wu ,&nbsp;Yanjun Wang ,&nbsp;Chao Wang ,&nbsp;Xiangdong Xue","doi":"10.1016/j.actbio.2024.12.059","DOIUrl":"10.1016/j.actbio.2024.12.059","url":null,"abstract":"<div><div>The activation of STING pathway has emerged as a promising strategy in cancer immunotherapy. However, challenges associated with unfavorable physicochemical properties and potential off-target toxicities have limited the application of STING agonists. Here, we develop an amphiphilic and cationic charged porphyrin-polymer to electrostatically load the STING agonist (MSA-2) within a micellar structure, thereby enhancing carrier compatibility and drug-loading content of MSA-2. Additionally, tumor-targeting ligands were functionalized onto the micelle to enhance specificity for tumor cells, aiming to significantly improve tumor accumulation while minimizing undesirable toxicity. The resultant tumor-targeting porphyrin micelle (TPC@M) seamlessly integrates three therapeutic mechanisms: i) tumor ablation via phototherapy; ii) robust activation of the STING pathway by MSA-2; iii) synergistic photo-/immuno- stimulations. TPC@M efficiently ablates primary tumors through phototherapy and further activates adaptive immune responses synergistically with MSA-2-induced innate immunity to suppress metastasis and prevent recurrence. Overall, we transformed a delivery-compromised therapeutic into a precise, stable, and safe nanomedicine that unleashes synergistic immunotherapeutic effects.</div></div><div><h3>Statement of significance</h3><div>This study addresses the urgent need for an efficient delivery system to fully harness the potential of the STING agonist MSA-2 in cancer immunotherapy. The cGAS-STING pathway plays a critical role in modulating anti-tumor immunity; however, the clinical application of MSA-2 has been hindered by its poor physicochemical properties and off-target effects. Our innovative approach introduces a tumor-targeting porphyrin-based polymeric micelle (TPC@M) that efficiently encapsulates MSA-2, overcoming compatibility issues associated with traditional nanocarriers. The TPC@M not only exhibits enhanced tumor targeting and reduced toxicity but also integrates phototherapy with immunotherapy, providing a synergistic strategy for cancer treatment. Our in vivo findings using 4T1 breast cancer mouse models demonstrate significant inhibition of tumor growth and prevention of metastasis, accompanied by a robust and long-lasting immune response.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 377-391"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercise impacts bone remodeling around bio-resorbable magnesium implants","authors":"Irene Rodriguez-Fernandez ,&nbsp;Thomas Bretschneider ,&nbsp;Andreas Menzel ,&nbsp;Omer Suljevic ,&nbsp;Nicole G. Sommer ,&nbsp;Annelie-M. Weinberg ,&nbsp;Christian Appel ,&nbsp;Marianne Liebi ,&nbsp;Ana Diaz ,&nbsp;Lukas Pircher ,&nbsp;Christian Hellmich ,&nbsp;Uwe Y. Schwarze ,&nbsp;Helga C. Lichtenegger ,&nbsp;Tilman A. Grünewald","doi":"10.1016/j.actbio.2024.12.008","DOIUrl":"10.1016/j.actbio.2024.12.008","url":null,"abstract":"<div><div>Physical exercise has been shown to induce positive reactions in bone healing but next to nothing is known about how it affects the nanostructure, in particular around implants. In this study, we established this link by using small-angle X-ray scattering tensor tomography (SASTT) to investigate nanostructural parameters in 3D such as mineral particle orientation and thickness. As a model system, rat femoral bone with a bio-resorbable implant (ultra-high purity magnesium) was used. One-half of the rats underwent treadmill exercise while the other half were moving freely in a cage. At two- and six-weeks post-surgery, rats were sacrificed, and samples were taken. Our results point to an earlier start and stronger remodeling when physical exercise is applied and to a stronger reorientation of the mineralized collagen fibers around the implant. This study reveals the nanostructural response of bone with bio-resorbable implants to physical exercise. Understanding this response is very important for designing post-surgery treatments.</div></div><div><h3>Statement of Significance</h3><div>Physical exercise is known to have beneficial effects on the human body and is often incorporated into the recovery process following orthopedic surgeries. While the response of bone to physical exercise is well-documented, the structural response of bone to early exercise after implant placement, particularly its impact on the nanostructure, has not been extensively studied. In this study, we identify the effects of physical exercise on the bone nanostructure and the remodeling process around a bioresorbable implant. These findings could help develop tailored physical exercise strategies for post-surgery recovery in patients.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 623-631"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical challenges and opportunities related to the biological responses experienced by indwelling and implantable bioelectronic medical devices","authors":"Kye J. Robinson ,&nbsp;Nicolas H. Voelcker ,&nbsp;Helmut Thissen","doi":"10.1016/j.actbio.2024.12.037","DOIUrl":"10.1016/j.actbio.2024.12.037","url":null,"abstract":"<div><div>Implantable electrodes have been utilized for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. While the underlying science related to the application of electrodes is a mature field, preclinical and clinical studies have demonstrated that there are still significant challenges in vivo associated with a lack of control over tissue-material interfacial interactions, especially over longer time frames. Herein we discuss the current challenges and opportunities for implantable electrodes and the associated bioelectronic interfaces across the clinical landscape with a focus on emerging technologies and the obstacles of biofouling, microbial colonization, and the foreign body response. Overcoming these challenges is predicted to open the door for a new generation of implantable medical devices and significant associated clinical impact.</div></div><div><h3>Statement of significance</h3><div>Implantable electrodes have been utilised for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. Next-generation bioelectronic implantable medical devices promise an explosion of new applications that have until this point in time been impossible to achieve. However, there are several persistent biological challenges hindering the realisation of these new applications. We present a clinical perspective on how these biological challenges have shaped the device market and clinical trial landscape. Specifically, we present statistical breakdowns of current device applications and discuss biofouling, the foreign body response, and microbial colonisation as the main factors that need to be addressed before a new generation of devices can be explored.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 49-64"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-Based biomaterials for anti-tumor therapy: Recent advances and perspectives","authors":"Shufang Zhang ,&nbsp;Shuping Peng","doi":"10.1016/j.actbio.2025.01.014","DOIUrl":"10.1016/j.actbio.2025.01.014","url":null,"abstract":"<div><div>Copper, an essential trace element, is integral to numerous metabolic pathways across biological systems. In recent years, copper-based biomaterials have garnered significant interest due to their superior biocompatibility and multifaceted functionalities, particularly in the treatment of malignancies such as sarcomas and cancers. On the one hand, these copper-based materials serve as efficient carriers for a range of therapeutic agents, including chemotherapeutic drugs, small molecule inhibitors, and antibodies, allowing them for precise delivery and controlled release triggered by specific modifications and stimuli. On the other hand, they can induce cell death through mechanisms such as ferroptosis, cuproptosis, apoptosis, and pyroptosis, or inhibit the proliferation and invasion of cancer cells via their outstanding properties. Furthermore, advanced design approaches enable these materials to support tumor imaging and immune activation. Despite this progress, the full scope of their functional capabilities remains to be fully elucidated. This review provides an overview of the anti-tumor functions, underlying mechanisms, and design strategies of copper-based biomaterials, along with their advantages and limitations. The aim is to provide insights into the design, study, and development of novel multifunctional biomaterials, with the ultimate goal of accelerating the clinical application of copper-based nanomaterials in cancer therapy.</div></div><div><h3>Statement of significance</h3><div>This study explores the groundbreaking potential of copper-based biomaterials in cancer therapy, uniquely combining biocompatibility with diverse therapeutic mechanisms such as targeted drug delivery and inhibition of cancer cells through specific cell death pathways. By enhancing tumor imaging and immune activation, copper-based nanomaterials have opened new avenues for cancer treatment. This review examines these multifunctional biomaterials, highlighting their advantages and current limitations while addressing gaps in existing research. The findings aim to accelerate clinical applications of these materials in the field of oncology, providing valuable insights for the design of next-generation copper-based therapies. Therefore, this work is highly relevant to researchers and practitioners focused on innovative cancer treatments.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 107-127"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodic mesoporous organosilica-loaded mincle agonists enhance the immunogenicity of COVID-19 subunit vaccines by dual activation of B cells and dendritic cells","authors":"Chunhe Zhang ,&nbsp;Fangshen Li ,&nbsp;Xin Yu ,&nbsp;Haochen Tian ,&nbsp;Yiyang Li ,&nbsp;Xinyao Liu ,&nbsp;Wenmo Liu ,&nbsp;Bin Yu ,&nbsp;Zhen-An Qiao ,&nbsp;Xianghui Yu","doi":"10.1016/j.actbio.2024.12.056","DOIUrl":"10.1016/j.actbio.2024.12.056","url":null,"abstract":"<div><div>Effective vaccination is crucial for intervening in the COVID-19 pandemic. However, with the continuous mutation of the SARS-CoV-2, existing vaccines including subunit vaccines cannot effectively prevent virus infections. Hence, there is an urgent need to enhance the immunogenicity of existing vaccines to induce a more potent and durable immune response. We previously found that periodic mesoporous organosilica (PMO) could act as a potential nanoadjuvant for subunit vaccines, eliciting potent antigen-specific germinal center (GC) responses by activating naïve B cells. In this study, we describe the design of PMO decorated with TDB, a potent Macrophage-induced C-type lectin (Mincle) agonist, to improve the adjuvanticity of PMO for COVID-19 vaccines. We found that the TDB@PMO adjuvant can effectively deliver antigens to lymph nodes and promote antigen uptake by immune cells. More importantly, the TDB@PMO adjuvant vaccine could activate the innate immune of both naïve B cells and dendritic cells via the Mincle signaling pathway, and further enhance the GC responses and resulting in potent SARS-CoV-2 specific humoral and cellular immune responses. Overall, we have developed an effective and safe nanoadjuvant platform, laying the foundation for the design and development of subunit vaccines against pathogens such as SARS-CoV-2.</div></div><div><h3>Statement of significance</h3><div>Adjuvants play a crucial role in enhancing the effectiveness of vaccines by boosting the immune response. The emergence of highly mutated viruses, such as coronaviruses, has presented new requirements for adjuvant design. This work designed a nanoadjuvant platform, TDB@PMO, to enhance the immune response of the COVID-19 subunit vaccine. The result demonstrated that TDB@PMO nanoadjuvant can simultaneously boost the activation effects of B cells and DC cells through the Mincle signaling pathway. Furthermore, immunization with TDB@PMO-RBD nanoadjuvanted vaccine in mice significantly enhanced germinal center responses and antibody production, while also eliciting a robust antigen-specific T cell immune response in spleen. This design provided a reference for the development of next-generation virus subunit vaccines.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 362-376"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial transfer of drug-loaded artificial mitochondria for enhanced anti-Glioma therapy through synergistic apoptosis/ferroptosis/immunogenic cell death","authors":"Mingzhu Song ,&nbsp;Jiayu Yuan ,&nbsp;Ge Zhang ,&nbsp;Mengdi Sun ,&nbsp;Yifei Zhang ,&nbsp;Xiangchen Su ,&nbsp;Ruizhen Lv ,&nbsp;Yuting Zhao ,&nbsp;Yijie Shi ,&nbsp;Liang Zhao","doi":"10.1016/j.actbio.2024.12.027","DOIUrl":"10.1016/j.actbio.2024.12.027","url":null,"abstract":"<div><div>Mitochondrial targeting in gliomas represents a novel therapeutic strategy with significant potential to enhance drug sensitivity by effectively killing glioma cells at the mitochondrial level. In this study, we developed artificial mitochondria derived from mitochondrial membrane-based nanovesicles, enabling precise mitochondrial targeting of doxorubicin (Dox) to selectively eradicate cancer cells by amplifying multiple cell death pathways. It was found that Dox-encapsulating mitochondria-based nanovesicles (DOX-MitoNVs) exhibited an extraordinary ability to penetrate the blood-brain barrier (BBB), specifically targeting gliomas. By targeting mitochondria instead of locating at the nucleus, DOX-MitoNVs not only amplified Dox mediated apoptosis effects through the overloading of intracellular Ca²⁺ but also intensified ferroptosis by generating reactive oxygen species (ROS). Furthermore, DOX-MitoNVs demonstrated a significant ability to modulate the tumor immune microenvironment, thereby inducing pronounced immunogenic cell death (ICD) effects. In summary, it presents a novel therapeutic strategy utilizing DOX-MitoNVs for precise mitochondrial targeting in gliomas, enhancing drug sensitivity, inducing multiple cell death pathways, and modulating the tumor immune microenvironment to promote immunogenic cell death.</div></div><div><h3>Statement of Significance</h3><div>Mitochondrial targeting in gliomas is a promising therapeutic strategy that enhances drug sensitivity by exploiting glioma cells' mitochondrial vulnerabilities. We engineered mitochondrial membrane-based nanovesicles as artificial mitochondria for precise mitochondrial targeting of Dox. This approach facilitates selective cancer cell eradication and amplifies multiple cell death pathways alongside immunogenic chemotherapy. Notably, DOX-MitoNVs effectively cross the BBB and specifically target gliomas. By focusing on mitochondria, Dox induces apoptosis and intensifies ferroptosis through ROS generation. Additionally, DOX-MitoNVs can transform the tumor immune microenvironment, promoting ICD. Overall, DOX-MitoNVs offer a promising platform for enhanced glioma therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 514-530"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-mediated efficient up-regulation of GSDMD-N to induce pyroptosis and enhance NK cell-based cancer immunotherapy","authors":"Zixian Huang ,&nbsp;Chunfang Wei ,&nbsp;Chen Yi ,&nbsp;Qiming Jiang ,&nbsp;Yong-Qiang Wang ,&nbsp;Yan Wang ,&nbsp;Tianshu Xu ,&nbsp;Nan Lu ,&nbsp;Zhiquan Huang ,&nbsp;Xiaoding Xu","doi":"10.1016/j.actbio.2024.12.061","DOIUrl":"10.1016/j.actbio.2024.12.061","url":null,"abstract":"<div><div>Natural killer (NK) cell-based immunotherapy has emerged as a safe and effective therapeutic modality for cancer treatment. However, therapeutic benefits can be only seen in hematological tumors (<em>e.g.</em>, leukemia) and the treatment of solid tumors is still less effective due to the immunosuppressive tumor microenvironment (TME)-induced poor infiltration and dysfunction of NK cells in tumor tissues. We herein developed a robust nucleus-targeted nanoparticle (NP) platform for systemic delivery of plasmid expressing the <em>N</em>-terminal domain of GSDMD (<em>i.e.</em>, pGSDMD-N) and augment of NK cell-based immunotherapy for oral squamous cell carcinoma (OSCC). This nanoplatform is made of a PEGylated poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) polymer and a nucleus-targeting peptide amphiphile (NTPA) that can complex pGSDMD-N. After intravenous administration, this nanoplatform could specifically deliver pGSDMD-N into the nuclei of OSCC cells, leading to their pyroptosis via up-regulating GSDMD-N expression. More importantly, this pyroptosis could boost NK cell-based immunotherapy via promoting the recruitment of NK cells into tumor tissues and enhancing their activation to further enhance the anticancer effect of the pGSDMD-N delivery system.</div></div><div><h3>Statement of significance</h3><div>: NK cell-based immunotherapy has made a significant breakthrough in the treatment of hematological tumors (<em>e.g.</em>, leukemia), but it is still less effective for solid tumors due to immunosuppressive tumor microenvironment (TME)-induced dysfunction of NK cells. We herein developed a nucleus-targeted nanoplatform for systemic delivery of plasmid expressing the <em>N</em>-terminal domain of gasdermin D (denoted pGSDMD-N) and augment of NK cell-based immunotherapy for oral squamous cell carcinoma (OSCC). This delivery system could not only induce the pyroptosis of OSCC cells, but also promote the secretion of functional chemokines (<em>e.g.</em>, CCL3) and cytokines (<em>e.g.</em>, IL-18) to boost NK cell-based immunotherapy. The strategy demonstrated herein could be a promising strategy to enhance the NK cell-based immunotherapy for solid tumors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 429-439"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}