María Sancho-Albero , Alessandra Decio , Reha Akpinar , Ada De Luigi , Raffaella Giavazzi , Luigi M. Terracciano , Luisa De Cola
{"title":"Melanoma extracellular vesicles membrane coated nanoparticles as targeted delivery carriers for tumor and lungs","authors":"María Sancho-Albero , Alessandra Decio , Reha Akpinar , Ada De Luigi , Raffaella Giavazzi , Luigi M. Terracciano , Luisa De Cola","doi":"10.1016/j.mtbio.2024.101433","DOIUrl":"10.1016/j.mtbio.2024.101433","url":null,"abstract":"<div><div>Targeting is the most challenging problem to solve for drug delivery systems. Despite the use of targeting units such as antibodies, peptides and proteins to increase their penetration in tumors the amount of therapeutics that reach the target is very small, even with the use of nanoparticles (NPs). Nature has solved the selectivity problem using a combination of proteins and lipids that are exposed on the cell membranes and are able to recognize specific tissues as demonstrated by cancer metastasis. Extracellular vesicles (EVs) have a similar ability in target only certain organs or to return to their original cells, showing home behavior. Here we report a strategy inspired by nature, using a combination of NPs and the targeting cell membranes of EVs. We implement the EV membranes, extracted by the EVs produced by melanoma B16-BL6 cells, as a coating of organosilica porous particles with the aim of targeting tumors and lung metastasis, while avoiding systemic effects and accumulation of the NPs in undesired organs. The tissue-specific fingerprint provided by the EVs-derived membranes from melanoma cells provides preferential uptake into the tumor and selective targeting of lungs. The ability of the EVs hybrid systems to behave as the natural EVs was demonstrated <em>in vitro</em> and <em>in vivo</em> in two different tumor models. As a proof of concept, the loading and release of doxorubicin, was investigated and its accumulation demonstrated in the expected tissues.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101433"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047202","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}
Jizhuang Ma , Wenhan Li , Yu Ding , Yongfeng Chen , Xiaoyu Huang , Tong Yu , Di Song , Haoran Niu , Bao Li , Huichao Xie , Keda Zhang , Tianzhi Yang , Xiaoyun Zhao , Xinggang Yang , Pingtian Ding
{"title":"Corrigendum to ‘Enhanced sclerotherapy for vascular malformations: A dual-mechanism approach using in-situ forming PATDs gel’ [Mater. Today Bio 29 (2024) 101376]","authors":"Jizhuang Ma , Wenhan Li , Yu Ding , Yongfeng Chen , Xiaoyu Huang , Tong Yu , Di Song , Haoran Niu , Bao Li , Huichao Xie , Keda Zhang , Tianzhi Yang , Xiaoyun Zhao , Xinggang Yang , Pingtian Ding","doi":"10.1016/j.mtbio.2024.101404","DOIUrl":"10.1016/j.mtbio.2024.101404","url":null,"abstract":"","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101404"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080596","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}
Cancan Li , Luowen Du , Yingying Xiao , Lei Fan , Quanli Li , Chris Ying Cao
{"title":"Multi-active phlorotannins boost antimicrobial peptide LL-37 to promote periodontal tissue regeneration in diabetic periodontitis","authors":"Cancan Li , Luowen Du , Yingying Xiao , Lei Fan , Quanli Li , Chris Ying Cao","doi":"10.1016/j.mtbio.2025.101535","DOIUrl":"10.1016/j.mtbio.2025.101535","url":null,"abstract":"<div><div>The bidirectional correlation between diabetes and periodontitis positions the latter as the most prevalent complication of the former. Rehabilitation of the periodontal tissues damaged by diabetic periodontitis presents a significant clinical challenge. The multifaceted nature of the pathogenesis of diabetic periodontitis necessitates a comprehensive approach in its treatment to mitigate its adverse effects. To address this, a temperature-sensitive hydrogel containing phlorotannins (PL) and antimicrobial peptide LL-37 was developed to shift the microenvironment of diabetic periodontitis from an exacerbated high-glycemic inflammatory state to a regenerative one. The addition of PL significantly enhanced the antimicrobial properties, stability, and safety of LL-37. Vitro experiments confirmed that PL/LL-37 had good biocompatibility and promoted osteogenic differentiation of bone. PL/LL-37 demonstrated antioxidant properties by scavenging DPPH free radicals and inhibiting NO production. Furthermore, PL/LL-37 effectively modulated macrophage polarization from a M1 phenotype to an M2 phenotype through NF-κB P-p65 inflammatory pathway, thereby reducing the release of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Interestingly, it could downregulate the AGE-RAGE signaling pathway, exerting a protective effect against diabetes. In addition, PL/LL-37 could attenuate inflammation levels, inhibit osteoclast production, promote bone regeneration, inhibit apoptosis and decrease RAGE levels in a rat model of diabetic periodontitis. These combined features synergistically accelerate diabetic periodontal bone regeneration. Consequently, PL/LL-37 emerges as a promising candidate for clinical treatment of diabetic periodontitis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101535"},"PeriodicalIF":8.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100611","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}
Manuel P. Kainz , Mathias Polz , Daniel Ziesel , Marta Nowakowska , Muammer Üçal , Sabine Kienesberger , Sophie Hasiba-Pappas , Raimund Winter , Nassim Ghaffari Tabrizi-Wizsy , Sarah Kager , Theresa Rienmüller , Julia Fuchs , Michele Terzano , Christian Baumgartner , Gerhard A. Holzapfel
{"title":"Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization","authors":"Manuel P. Kainz , Mathias Polz , Daniel Ziesel , Marta Nowakowska , Muammer Üçal , Sabine Kienesberger , Sophie Hasiba-Pappas , Raimund Winter , Nassim Ghaffari Tabrizi-Wizsy , Sarah Kager , Theresa Rienmüller , Julia Fuchs , Michele Terzano , Christian Baumgartner , Gerhard A. Holzapfel","doi":"10.1016/j.mtbio.2025.101508","DOIUrl":"10.1016/j.mtbio.2025.101508","url":null,"abstract":"<div><div>Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship between scaffold mechanical properties and reactions at the biological interface remains poorly understood. This study examines the attachment and integration of soft hydrogels on the CAM using an accessible <em>ex ovo</em> system. Composite hydrogels of polyvinyl alcohol and Phytagel were fabricated by sterile freeze-thawing. CAM assays, as an alternative to traditional <em>in vivo</em> models, enabled the evaluation of the compatibility, attachment, and biointegration of hydrogels with three distinct compositions. The mechanomimetic properties of the hydrogels were assessed through cyclic compression–tension tests, with nominal peak stresses ranging from <span><math><mrow><mn>0</mn><mo>.</mo><mn>26</mn></mrow></math></span> to <span><math><mrow><mn>2</mn><mo>.</mo><mn>82</mn></mrow></math></span> <!--> <!-->kPa in tension and <span><math><mrow><mo>−</mo><mn>0</mn><mo>.</mo><mn>33</mn></mrow></math></span> to <span><math><mrow><mo>−</mo><mn>2</mn><mo>.</mo><mn>92</mn></mrow></math></span> <!--> <!-->kPa in compression. Mechanical attachment to the CAM was measured by pull-off tests after five days of incubation. On the first day, the interface strength was similar for all hydrogel compositions. On day <span><math><mn>5</mn></math></span>, softer hydrogels showed the greatest increase (<span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>008</mn></mrow></math></span>), followed by intermediate hydrogels (<span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>020</mn></mrow></math></span>), while the denser hydrogels showed negligible changes (<span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>073</mn></mrow></math></span>). Histological analyses revealed cell infiltration in <span><math><mrow><mn>100</mn></mrow></math></span>% of soft, <span><math><mrow><mn>75</mn></mrow></math></span>% of intermediate, and <span><math><mrow><mn>13</mn></mrow></math></span>% of dense hydrogels, suggesting that softer hydrogels integrate better into the CAM by facilitating cell migration and enhancing interface strength. Chicken embryo survival rates and cytotoxicity assays confirmed the biocompatibility of the hydrogels and supported their potential for use in soft, hydrated three-dimensional scaffolds that mimic tissue environments in dynamic biological systems.</div><div><strong>Statement of significance</strong> Current research on soft scaffold materials for cell cultures often overlooks the critical relationship between mechanical properties and biological integration of these materials with host tissues. Although hydrogels, as soft porous materials, hold promise for creating physiologically relevant environments, the mechanisms driv","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101508"},"PeriodicalIF":8.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096653","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}
Linzhong Yang , Yuanchen Liu , Cheng Tao , Zichen Cao , Shilin Guo , Zheng Wei , Yanyi Wang , Tao Liu , Lin Chen , Ke Xiong , Xingyu Luo , Jianchuan Ran , Wei Han
{"title":"Bionic nanovesicles sequentially treat flaps with different durations of ischemia by thrombolysis and prevention of ischemia-reperfusion injury","authors":"Linzhong Yang , Yuanchen Liu , Cheng Tao , Zichen Cao , Shilin Guo , Zheng Wei , Yanyi Wang , Tao Liu , Lin Chen , Ke Xiong , Xingyu Luo , Jianchuan Ran , Wei Han","doi":"10.1016/j.mtbio.2025.101529","DOIUrl":"10.1016/j.mtbio.2025.101529","url":null,"abstract":"<div><div>Flap transplantation is a critical part of the recovery process for patients who have undergone tumor resection. However, the process of ischemia-reperfusion injury during flap transplantation and the resulting high-risk thrombotic microenvironment are unavoidable. In this study, based on an in-depth investigation of the ischemia time and prognosis of transplanted flaps, we propose a treatment strategy using sequential thrombolysis and ischemia-reperfusion injury prevention tailored to the ischemia time. This approach is designed to minimize the likelihood of thrombus formation and to clear the intravascular inflammatory microenvironment, with the aim of preventing and salvaging ischemic flaps. Specifically, we have successfully constructed a clinical-grade bionic vesicle, UK-PBNZ@PM, a system that cleverly incorporates drug components that have been widely used in clinical applications, thereby demonstrating a high degree of clinical translational potential. Prussian blue nano-enzymes (PBNZ) are the core component and demonstrate remarkable efficacy against ischemia-reperfusion injury due to their excellent biocompatibility, robust reactive oxygen species (ROS) scavenging capacity and anti-inflammatory properties. At the same time, urokinase (UK), a key pharmaceutical agent in antithrombotic therapy, has been effectively incorporated into the system, enhancing its ability to prevent and treat thrombosis. In addition, the integration of a platelet membrane (PM) has endowed the bionic vesicles with precise targeting and delivery capabilities, ensuring that the drugs can reach the lesion directly and facilitate efficient and precise release. The experimental results demonstrated that an ischemia-timed strategy can not only efficiently promote thrombolysis, but also effectively remove harmful elements in the microenvironment of ischemia-reperfusion injury. This discovery represents a new and promising approach to the treatment of thrombosis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101529"},"PeriodicalIF":8.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096652","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}
Di Wu , Wenjie Ma , Liucheng Wang , Chengcheng Long , Silin Chen , Jingyu Liu , Yiguan Qian , Jun Zhao , Changcheng Zhou , Ruipeng Jia
{"title":"Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury","authors":"Di Wu , Wenjie Ma , Liucheng Wang , Chengcheng Long , Silin Chen , Jingyu Liu , Yiguan Qian , Jun Zhao , Changcheng Zhou , Ruipeng Jia","doi":"10.1016/j.mtbio.2025.101528","DOIUrl":"10.1016/j.mtbio.2025.101528","url":null,"abstract":"<div><div>Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular vesicles (EVs) hold promise as cell-free therapies for treating renal IRI; however, their efficacy is limited by low delivery efficiency. In this study, we developed neutrophils (NEs) membrane-modified EVs (N-EVs) by exploiting the natural properties of NEs to target damaged endothelium. N-EVs inherited the characteristic membrane proteins of NEs along with the biological functions of EPCs-EVs. Results from <em>in vitro</em> and <em>in vivo</em> experiments demonstrated that N-EVs significantly enhanced the targeting efficiency of EVs towards IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, N-EVs effectively promoted the proliferation, migration, and tube-formation abilities of injured endothelial cells (ECs) and contributed to overall renal function improvement in IRI kidneys through targeted delivery of miR-21-5p. Additionally, N-EVs could restore damaged endothelial integrity, reduce cytokine release, and inhibit leukocyte infiltration, hence alleviating renal inflammation. In conclusion, our accessible engineering approach represents a promising strategy for treating renal IRI. Furthermore, this membrane hybrid modification can be tailored and optimized for broader applications in treating other diseases.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101528"},"PeriodicalIF":8.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096651","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":"Nanomaterials for targeted therapy of kidney diseases: Strategies and advances","authors":"Zhiwen Wang, Chun Zhang","doi":"10.1016/j.mtbio.2025.101534","DOIUrl":"10.1016/j.mtbio.2025.101534","url":null,"abstract":"<div><div>The treatment and management of kidney diseases pose a significant global burden. Due to the presence of blood circulation barriers and glomerular filtration barriers, drug therapy for kidney diseases faces challenges such as poor renal targeting, short half-life, and severe systemic side effects, severely hindering therapeutic progress. Therefore, the research and development of kidney-targeted therapeutic agents is of great clinical significance. In recent years, the application of nanotechnology in the field of nephrology has shown potential for revolutionizing the diagnosis and treatment of kidney diseases. Carefully designed nanomaterials can exhibit optimal biological characteristics, influencing various aspects such as circulation, retention, targeting, and excretion. Rationally designing and modifying nanomaterials based on the anatomical structure and pathophysiological environment of the kidney to achieve highly specific kidney-targeted nanomaterials or nanodrug delivery systems is both feasible and promising. Based on the targeted therapy of kidney diseases, this review discusses the advantages and limitations of current nanomedicine in the targeted therapy of kidney diseases, and summarizes the application and challenges of current renal active/passive targeting strategies, in order to further promote the development of kidney-targeted nanomedicine through a preliminary summary of previous studies and future prospects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101534"},"PeriodicalIF":8.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100616","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}
Jing Han , Zhao Li , Jing Du , Qun Zhang , Shaohua Ge , Hong Liu , Baojin Ma
{"title":"Natural collagen scaffold with intrinsic piezoelectricity for enhanced bone regeneration","authors":"Jing Han , Zhao Li , Jing Du , Qun Zhang , Shaohua Ge , Hong Liu , Baojin Ma","doi":"10.1016/j.mtbio.2025.101532","DOIUrl":"10.1016/j.mtbio.2025.101532","url":null,"abstract":"<div><div>Materials-mediated piezoelectric signals have been widely applied in bone regeneration. Collagen is the most abundant protein in the human body, and native collagen with complete tertiary structure shows efficient piezoelectricity. However, the traditional collagen scaffolds are lack of piezoelectricity due to the destruction of the complete tertiary structure. Here, natural collagen scaffolds with the complete tertiary structure were prepared. Alkali treatment made the collagen scaffold lose piezoelectricity. The collagen with/without piezoelectricity (PiezoCol/NCol) scaffolds both possessed good cytocompatibility and promoted cell adhesion. After being implanted subcutaneously, the NCol scaffold almost did not affect bone regeneration with/without ultrasound treatment. However, under ultrasound treatment, the PiezoCol scaffold promoted the new bone formation with enhanced osteogenic differentiation, angiogenesis, and neural differentiation, meaning that piezoelectricity endows collagen with satisfactory promotion for bone regeneration. Meanwhile, the PiezoCol scaffold can also accelerate bone formation without ultrasound treatment, which should be attributed to the daily exercise-caused weak piezoelectric stimulation. Further, the proteomic analysis revealed the mechanism by which the PiezoCol scaffold promoted bone tissue formation via mainly upregulating the PI3K-Akt signaling pathway. This study provides a new strategy to enhance the osteoinduction of collagen scaffold for bone regeneration by maintaining intrinsic piezoelectricity.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101532"},"PeriodicalIF":8.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100901","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":"Functional poly(ether-ketone-ketone) composite scaffold with enhanced cell-material interaction, anti-inflammatory and osteogenesis for facilitating osteointegration and bone regeneration","authors":"Qianwen Yang, Anbei Chen, Xin Zhang, Zhaoying Wu, Chao Zhang","doi":"10.1016/j.mtbio.2025.101533","DOIUrl":"10.1016/j.mtbio.2025.101533","url":null,"abstract":"<div><div>Bone defects resulting from trauma or disease remain a significant challenge in clinical practice, often requiring prolonged treatment. Poly(ether-ketone-ketone) (PEKK) is a commonly used implant material due to its excellent biocompatibility and mechanical properties, which are similar to those of bone. However, its biological inertness leads to poor anti-inflammatory and osteointegration properties, significantly hindering the bone repair process. In this study, a cryogel filled - PEKK/bioglass (BG) composite scaffold (SPBC) was prepared <em>via</em> 3D printing to provide immunomodulatory and bone integration performance. Compared with untreated PEKK, SPBC exhibited significant enhancements in surface properties, including higher hydrophilicity and roughness. Additionally, SPBC enhanced the adsorption of fibronectin and vitronectin on the scaffold surface and regulated the maturation of cytoskeleton and adhesion plaques by increasing the phosphorylation level of FAK at Y397, thereby promoting cell adhesion and spreading. Due to the release of bioactive ions, SPBC can significantly promote the polarization of RAW264.7 cells towards M2 and the secretion of anti-inflammatory cytokines, while also enhancing the proliferation and differentiation of rat mesenchymal stem cells (rMSCs) <em>in vitro</em>. Furthermore, the <em>in vivo</em> results confirmed the enhanced anti-inflammatory properties and the integration of SPBC with the host tissue. In summary, after surface modification and cryogel filling, SPBC demonstrated excellent anti-inflammatory and bone integration abilities, presenting potential for clinical application as an orthopedic implant scaffold.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101533"},"PeriodicalIF":8.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096650","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}
Tao Xu , Kehan Liu , Shuqi Mi , Yao Yao , Mengyao Zhang , Shujuan Xue , Feng Zhi , Sally-Ann Cryan , Dawei Ding
{"title":"Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy","authors":"Tao Xu , Kehan Liu , Shuqi Mi , Yao Yao , Mengyao Zhang , Shujuan Xue , Feng Zhi , Sally-Ann Cryan , Dawei Ding","doi":"10.1016/j.mtbio.2025.101530","DOIUrl":"10.1016/j.mtbio.2025.101530","url":null,"abstract":"<div><div>Low immunogenicity and immunosuppressive tumor microenvironment (TME) are two pivotal factors restricting tumor immunotherapy. Photodynamic therapy (PDT) directly destroys cancer cells by producing reactive oxygen species (ROS), and enhances the immunogenicity of \"cold\" tumors by inducing immunogenic cell death (ICD), thereby promoting T cell development against tumors. However, PDT also deteriorates immunosuppression through overactivating the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. To this end, biocompatible albumin nanoassemblies co-delivering IR780 and diclofenac are herein developed for enhanced therapy against triple-negative breast cancer. PDT-exacerbated PGE2 overexpression is effectively abolished by diclofenac-mediated COX-2 inhibition, which reprograms immunosuppressive TME <em>via</em> downregulating the infiltration of various immunosuppressive cells and their cytokine secretion to enhance effector T cell infiltration. Consequently, the enhanced antitumor immunity effectively inhibits tumor growth, prevents the recurrency and metastasis, and remarkably boosts the treatment efficacy of PD-L1 blockade. This study sets an intriguing example for overcoming the COX-2/PGE2 pathway-exacerbated immunosuppression alongside immune activation, thus enhancing synergistic cancer immunotherapy potentiated by various ROS-producing therapies (e.g., PDT and radiotherapy) and chemotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101530"},"PeriodicalIF":8.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100609","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}