Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.09.014
Qi Shang , Chenwei Jiang , Xiaolong Wang , Mingmei Guo , Jing Liu , Zhedong Jin , Yunsheng Yuan , Feihu Wang
Vaccines represent one of the most potent strategies for protecting humans from the threat of infectious diseases. Conventional vaccines elicit acquired immunity by mimicking pathogen characteristics; however, their protective efficacy is limited by inadequate spatiotemporal control of antigen delivery, resulting in suboptimal antigen exposure in lymphoid tissues and transient adaptive immune activation. Here, we developed a self-assembling peptide-based supramolecular hydrogel vaccine to establish a localized immune niche, demonstrating its remarkable efficacy in inducing durable and potent immunity against infectious diseases. We found that this in situ-formed supramolecular hydrogel vaccine serves as a reservoir for antigens and adjuvants while recruiting antigen-presenting dendritic cells (DCs) to accumulate within the scaffold. With the aid of adjuvant, the DCs exhibit enhanced antigen processing and presentation, creating an immunologically active niche that triggers robust B cell and T cell responses. Following a single vaccination, mice immunized with the hydrogel vaccine developed robust humoral immunity and sustained antibody production for 112 days, achieving potent neutralization activity. This study offers a novel approach to spatiotemporal control of vaccine responses that enables durable and enhanced immunity against infectious diseases.
{"title":"Construction of a localized immune niche via supramolecular hydrogel vaccine to elicit durable and enhanced immunity against infectious diseases","authors":"Qi Shang , Chenwei Jiang , Xiaolong Wang , Mingmei Guo , Jing Liu , Zhedong Jin , Yunsheng Yuan , Feihu Wang","doi":"10.1016/j.apsb.2025.09.014","DOIUrl":"10.1016/j.apsb.2025.09.014","url":null,"abstract":"<div><div>Vaccines represent one of the most potent strategies for protecting humans from the threat of infectious diseases. Conventional vaccines elicit acquired immunity by mimicking pathogen characteristics; however, their protective efficacy is limited by inadequate spatiotemporal control of antigen delivery, resulting in suboptimal antigen exposure in lymphoid tissues and transient adaptive immune activation. Here, we developed a self-assembling peptide-based supramolecular hydrogel vaccine to establish a localized immune niche, demonstrating its remarkable efficacy in inducing durable and potent immunity against infectious diseases. We found that this <em>in situ</em>-formed supramolecular hydrogel vaccine serves as a reservoir for antigens and adjuvants while recruiting antigen-presenting dendritic cells (DCs) to accumulate within the scaffold. With the aid of adjuvant, the DCs exhibit enhanced antigen processing and presentation, creating an immunologically active niche that triggers robust B cell and T cell responses. Following a single vaccination, mice immunized with the hydrogel vaccine developed robust humoral immunity and sustained antibody production for 112 days, achieving potent neutralization activity. This study offers a novel approach to spatiotemporal control of vaccine responses that enables durable and enhanced immunity against infectious diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 470-483"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941494","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.048
Haiyan Wang , Zhi-Chao Sun , Chunlei Dai , Ran Liao , Ran Lin , Liying Wang , Wenjun Fu , Ruhe Zhang , Danwen Zheng , Zhongde Zhang , Jun Wu , Yuntao Liu
Acute respiratory distress syndrome (ARDS) is a life-threatening disease. In the clinical management of ARDS, current treatments such as glucocorticoids and protease inhibitors encounter significant challenges due to their high toxicity, limited administration routes, or poor targeting. These limitations highlight the urgent need for innovative therapeutic strategies. Songorine (Son), a compound derived from the herb Aconitum carmichaelii Debeaux, possesses good antioxidant and anti-inflammatory properties, exhibiting great potential for treating ARDS. However, its clinical application is partially constrained by low aqueous solubility and uncertain efficacy for ARDS. In this study, we developed a lung-targeted lipid nanomedicine by encapsulating Son in dipalmitoyl phosphatidylcholine (DPPC) liposomes (Son@liposome, Son-lipo). In a lipopolysaccharide-induced ARDS mouse model, we demonstrated that Son-lipo effectively targeted inflamed lung tissues with commendable biocompatibility. Further, Son-lipo significantly alleviated multiple ARDS phenotypes such as endothelial barrier damage, lung edema, pulmonary dysfunction, and alveolar lesion, which involved uncontrolled inflammation, oxidative stress, and cell apoptosis. RNA sequencing and Western blotting analyses revealed that Son-lipo inhibited the activation of the TLR4/NF-κB/NLRP3 pathway responsible for ARDS. In conclusion, our study successfully developed an inhalable lipid-nanomedicine (Son-lipo) as a novel therapeutic strategy for ARDS. It elucidates the formulation's ability to mitigate ARDS by repairing the endothelial barrier and reversing the inflammatory microenvironment, thereby providing a promising candidate drug for improving clinical management of ARDS.
{"title":"Inhalable songorine-integrated lipid nanomedicine for targeted ARDS therapy via repairing endothelial barrier and inactivating NLRP3 inflammasome","authors":"Haiyan Wang , Zhi-Chao Sun , Chunlei Dai , Ran Liao , Ran Lin , Liying Wang , Wenjun Fu , Ruhe Zhang , Danwen Zheng , Zhongde Zhang , Jun Wu , Yuntao Liu","doi":"10.1016/j.apsb.2025.10.048","DOIUrl":"10.1016/j.apsb.2025.10.048","url":null,"abstract":"<div><div>Acute respiratory distress syndrome (ARDS) is a life-threatening disease. In the clinical management of ARDS, current treatments such as glucocorticoids and protease inhibitors encounter significant challenges due to their high toxicity, limited administration routes, or poor targeting. These limitations highlight the urgent need for innovative therapeutic strategies. Songorine (Son), a compound derived from the herb <em>Aconitum carmichaelii</em> Debeaux, possesses good antioxidant and anti-inflammatory properties, exhibiting great potential for treating ARDS. However, its clinical application is partially constrained by low aqueous solubility and uncertain efficacy for ARDS. In this study, we developed a lung-targeted lipid nanomedicine by encapsulating Son in dipalmitoyl phosphatidylcholine (DPPC) liposomes (Son@liposome, Son-lipo). In a lipopolysaccharide-induced ARDS mouse model, we demonstrated that Son-lipo effectively targeted inflamed lung tissues with commendable biocompatibility. Further, Son-lipo significantly alleviated multiple ARDS phenotypes such as endothelial barrier damage, lung edema, pulmonary dysfunction, and alveolar lesion, which involved uncontrolled inflammation, oxidative stress, and cell apoptosis. RNA sequencing and Western blotting analyses revealed that Son-lipo inhibited the activation of the TLR4/NF-<em>κ</em>B/NLRP3 pathway responsible for ARDS. In conclusion, our study successfully developed an inhalable lipid-nanomedicine (Son-lipo) as a novel therapeutic strategy for ARDS. It elucidates the formulation's ability to mitigate ARDS by repairing the endothelial barrier and reversing the inflammatory microenvironment, thereby providing a promising candidate drug for improving clinical management of ARDS.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 596-615"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941501","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.11.020
Tianhao Wang , Yining Hu , Wenbo Guo , Haoran Li , Menglei Wang , Bojin Chen , Hudong Bao , Meng Gao , Xiang Li , Qian Chen , Minjie Shen , Xin Shao , Jie Liao , Xiaohui Fan
{"title":"An integrated resource for ischemic heart disease defines hallmarks and heterogeneity across time and space","authors":"Tianhao Wang , Yining Hu , Wenbo Guo , Haoran Li , Menglei Wang , Bojin Chen , Hudong Bao , Meng Gao , Xiang Li , Qian Chen , Minjie Shen , Xin Shao , Jie Liao , Xiaohui Fan","doi":"10.1016/j.apsb.2025.11.020","DOIUrl":"10.1016/j.apsb.2025.11.020","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 642-646"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941464","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.11.005
Zeyu Xiao , Jiaxin Yuan , Qing Wu , Juan Qin , Yiming Liu , Siqi Zhang , Bo Sun , Ruoxue Dai , Pingping Zhang , Ni Shao , Shuang Che , Yin He , Jifeng Chen , Shunqian Wen , Kuan Hu , Duo Wang , Liangping Luo
Insufficient radiofrequency ablation (IRFA) of hepatocellular carcinoma (HCC) leads to alterations in epigenetic properties such as N6-methyladenosine (m6A) RNA methylation in tumor cells, which creates an immune-suppressive tumor microenvironment capable of promoting residual tumor growth and recurrence and affecting the efficacy of RFA. In this study, the constructed STM-Mn@OMVs, which were produced through the rational functionalisation of bacterial-derived OMVs with Mn2+ ions and the methylation inhibitor STM2457, were found to effectively activate antitumor immunity. Our study shows that STM-Mn@OMVs can effectively promote dendritic cells (DCs) maturation, T cell activation, and STING pathway activation after endocytosis by cells, thus promoting immune cell infiltration. The STM-Mn@OMVs were able to promote cellular pyroptosis and synergistically activate the STING pathway. Furthermore, STM-Mn@OMVs promoted the increase of M1 macrophage phenotype in tumor-associated macrophages (TAMs) by reducing the infiltration of immunosuppressive cell populations such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), thus reversing the suppressive immune microenvironment after IRFA to some extent. Ultimately, the growth of residual tumors was inhibited. In addition, the biosafety of STM-Mn@OMVs was demonstrated in this study. Therefore, the STM-Mn@OMVs constructed in this study have great potential for application in the field of RFA and immunotherapy for HCC.
{"title":"Engineered bacterial extracellular vesicles mediate pyroptosis to counteract m6A methylation-based immunosuppression after insufficient radiofrequency ablation of hepatocellular carcinoma","authors":"Zeyu Xiao , Jiaxin Yuan , Qing Wu , Juan Qin , Yiming Liu , Siqi Zhang , Bo Sun , Ruoxue Dai , Pingping Zhang , Ni Shao , Shuang Che , Yin He , Jifeng Chen , Shunqian Wen , Kuan Hu , Duo Wang , Liangping Luo","doi":"10.1016/j.apsb.2025.11.005","DOIUrl":"10.1016/j.apsb.2025.11.005","url":null,"abstract":"<div><div>Insufficient radiofrequency ablation (IRFA) of hepatocellular carcinoma (HCC) leads to alterations in epigenetic properties such as <em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA methylation in tumor cells, which creates an immune-suppressive tumor microenvironment capable of promoting residual tumor growth and recurrence and affecting the efficacy of RFA. In this study, the constructed STM-Mn@OMVs, which were produced through the rational functionalisation of bacterial-derived OMVs with Mn<sup>2+</sup> ions and the methylation inhibitor STM2457, were found to effectively activate antitumor immunity. Our study shows that STM-Mn@OMVs can effectively promote dendritic cells (DCs) maturation, T cell activation, and STING pathway activation after endocytosis by cells, thus promoting immune cell infiltration. The STM-Mn@OMVs were able to promote cellular pyroptosis and synergistically activate the STING pathway. Furthermore, STM-Mn@OMVs promoted the increase of M1 macrophage phenotype in tumor-associated macrophages (TAMs) by reducing the infiltration of immunosuppressive cell populations such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), thus reversing the suppressive immune microenvironment after IRFA to some extent. Ultimately, the growth of residual tumors was inhibited. In addition, the biosafety of STM-Mn@OMVs was demonstrated in this study. Therefore, the STM-Mn@OMVs constructed in this study have great potential for application in the field of RFA and immunotherapy for HCC.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 522-538"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941498","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.020
Huanhuan Pang , Honglin Chen , Peng Chen , Xu Wei , Hongda Liu , Xueling He , Yang Yang , Junzhe Zhang , Dianfei Li , Linlin Lou , Wen Xie , Chong Qiu , Fei Xia , Qiuyan Guo , Shengnan Shen , Qiaoli Shi , Weiguang Li , Guang Han , Xijun Wang , Jigang Wang , Chengchao Xu
Sepsis is a life-threatening disease caused by the dysregulated host immune response to infection, which eventually leads to multi-organ failure. Current therapeutic strategies rely heavily on antibiotics. However, conventional antimicrobial therapy often leads to antibiotic abuse and resistance. Therefore, it is of utmost importance to develop new agents for treating sepsis. Here, we demonstrated that gambogenic acid (GNA) not only restricted the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages but also attenuated the inflammatory response and organ damage in septic mice. By using the activity-based protein profiling (ABPP) strategy, we identified 30 potential target proteins of GNA. Among these potential targets, we found that GNA directly bound to the Cys684 residue of hexokinase 1 (HK1) and affected its enzyme activity and cellular localization. These findings were confirmed by the cellular thermal shift assay (CETSA), bio-layer interferometry (BLI), and single-site mutation experiments. Functionally, siHK1 alleviated the Warburg effect, suppressed the activation of NLRP3 inflammasome, and eventually suppressed the release of inflammatory cytokines. Taken together, our findings demonstrated that GNA could attenuate inflammation by alleviating HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis and could serve as a novel therapeutic agent for sepsis and inflammatory disorders.
{"title":"Gambogenic acid ameliorates inflammation by inhibiting HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis","authors":"Huanhuan Pang , Honglin Chen , Peng Chen , Xu Wei , Hongda Liu , Xueling He , Yang Yang , Junzhe Zhang , Dianfei Li , Linlin Lou , Wen Xie , Chong Qiu , Fei Xia , Qiuyan Guo , Shengnan Shen , Qiaoli Shi , Weiguang Li , Guang Han , Xijun Wang , Jigang Wang , Chengchao Xu","doi":"10.1016/j.apsb.2025.10.020","DOIUrl":"10.1016/j.apsb.2025.10.020","url":null,"abstract":"<div><div>Sepsis is a life-threatening disease caused by the dysregulated host immune response to infection, which eventually leads to multi-organ failure. Current therapeutic strategies rely heavily on antibiotics. However, conventional antimicrobial therapy often leads to antibiotic abuse and resistance. Therefore, it is of utmost importance to develop new agents for treating sepsis. Here, we demonstrated that gambogenic acid (GNA) not only restricted the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages but also attenuated the inflammatory response and organ damage in septic mice. By using the activity-based protein profiling (ABPP) strategy, we identified 30 potential target proteins of GNA. Among these potential targets, we found that GNA directly bound to the Cys684 residue of hexokinase 1 (HK1) and affected its enzyme activity and cellular localization. These findings were confirmed by the cellular thermal shift assay (CETSA), bio-layer interferometry (BLI), and single-site mutation experiments. Functionally, siHK1 alleviated the Warburg effect, suppressed the activation of NLRP3 inflammasome, and eventually suppressed the release of inflammatory cytokines. Taken together, our findings demonstrated that GNA could attenuate inflammation by alleviating HK1-mediated Warburg effect and NLRP3 inflammasome activation in sepsis and could serve as a novel therapeutic agent for sepsis and inflammatory disorders.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 337-351"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941526","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.033
Liang Liao , Qiang Wang , Zhengyang Gao , Jiayao Liu , Yuxuan Tong , Xin Chen , Jin Zhu , Jian Li , Jinlian Wei
{"title":"Rifamycin O as a novel CRBN ligand for targeted degradation of IKZF1/3 proteins in hematopoietic malignancies","authors":"Liang Liao , Qiang Wang , Zhengyang Gao , Jiayao Liu , Yuxuan Tong , Xin Chen , Jin Zhu , Jian Li , Jinlian Wei","doi":"10.1016/j.apsb.2025.10.033","DOIUrl":"10.1016/j.apsb.2025.10.033","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 647-650"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941465","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.002
Nan Lin , Keqin Tan , Yuhao Wei , Songtao Xie , Jiaming Liu , Xuelei Ma
The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug delivery systems, innovative nanoscale vaccines, and strategies for reprogramming immunosuppressive cells. Furthermore, the review explores the clinical applicability and prospects of personalized nanomedicine, highlighting its increasingly prominent role in tailored cancer therapeutics.
{"title":"The progress and perspective of nanomedicine in modulating the tumor immune microenvironment","authors":"Nan Lin , Keqin Tan , Yuhao Wei , Songtao Xie , Jiaming Liu , Xuelei Ma","doi":"10.1016/j.apsb.2025.10.002","DOIUrl":"10.1016/j.apsb.2025.10.002","url":null,"abstract":"<div><div>The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug delivery systems, innovative nanoscale vaccines, and strategies for reprogramming immunosuppressive cells. Furthermore, the review explores the clinical applicability and prospects of personalized nanomedicine, highlighting its increasingly prominent role in tailored cancer therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 137-168"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941479","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.038
Fangke Zhang , Tao Ding , Jiancheng Zheng , Nan Li , Zechuan Li , Xuefei Wang , Yawei Du , Weiguo Hu , Wenguo Cui , Weisheng Guo
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that requires long-term pharmacological management. Melittin, a peptide derived from bee venom, has shown promising therapeutic efficacy for RA by modulating immune balance. Given the critical role of the gut in immune regulation, oral administration of melittin could have significant clinical implications. However, this approach faces substantial challenges, including degradation by gastric fluids and off-target adverse effects, which compromise its efficacy and safety. To address these limitations, we developed an innovative orally administered, gut-targeted micro-nano system (SPM/AlgL) inspired by bacterial colonies. Herein, gas-shearing microfluidics is leveraged to monodisperse sialic acid-decorated peptide nanomedicines within calcium alginate microgels. These microspheres are then coated with probiotic biofilms, leveraging their acid resistance and intestinal adhesion properties. The biofilm coating effectively protects melittin from gastric degradation and enhances its accumulation in the mesenteric lymph nodes, thereby improving its targeting ability to inflammatory sites and reducing adverse effects. By modulating the Th1/Th2 and Th17/Treg ratios in the mesenteric lymph nodes and spleen tissues, this system successfully alleviates immune responses and efficiently mitigates the progression of arthritis. Overall, this oral therapeutic strategy demonstrates significant potential for advancing the immunotherapy of RA and other systemic autoimmune diseases.
{"title":"Oral administration of probiotic colony-like micro-nano system for immunoregulation of rheumatoid arthritis","authors":"Fangke Zhang , Tao Ding , Jiancheng Zheng , Nan Li , Zechuan Li , Xuefei Wang , Yawei Du , Weiguo Hu , Wenguo Cui , Weisheng Guo","doi":"10.1016/j.apsb.2025.10.038","DOIUrl":"10.1016/j.apsb.2025.10.038","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that requires long-term pharmacological management. Melittin, a peptide derived from bee venom, has shown promising therapeutic efficacy for RA by modulating immune balance. Given the critical role of the gut in immune regulation, oral administration of melittin could have significant clinical implications. However, this approach faces substantial challenges, including degradation by gastric fluids and off-target adverse effects, which compromise its efficacy and safety. To address these limitations, we developed an innovative orally administered, gut-targeted micro-nano system (SPM/AlgL) inspired by bacterial colonies. Herein, gas-shearing microfluidics is leveraged to monodisperse sialic acid-decorated peptide nanomedicines within calcium alginate microgels. These microspheres are then coated with probiotic biofilms, leveraging their acid resistance and intestinal adhesion properties. The biofilm coating effectively protects melittin from gastric degradation and enhances its accumulation in the mesenteric lymph nodes, thereby improving its targeting ability to inflammatory sites and reducing adverse effects. By modulating the Th1/Th2 and Th17/Treg ratios in the mesenteric lymph nodes and spleen tissues, this system successfully alleviates immune responses and efficiently mitigates the progression of arthritis. Overall, this oral therapeutic strategy demonstrates significant potential for advancing the immunotherapy of RA and other systemic autoimmune diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 444-457"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941492","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}
Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.10.042
Feng Fang , Min Su , Xue Liu , Jing Chen , Qiwen Liu , Xinran Li , Xuanbo Zhang , Yuanyuan Chen , Huijiao Fu , Zhengchai Chen , Cao Zhou , Xuzi Cai , Zhengfen Li , Zhiqiang Yu , Xuefeng Wang
Ovarian cancer remains a formidable therapeutic challenge due to its high propensity for abdominal metastasis, recurrence, and the presence of an immunosuppressive tumor microenvironment. To overcome these obstacles, we developed a self-assembled nanoplatforms (OSN) by integrating a near-infrared semiconducting polymer with an oxaliplatin(IV) prodrug. This multifunctional design enables a synergistic triple-modality therapy—photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy—within a single nanoparticle, effectively enhancing immunogenic cell death (ICD) and systemic antitumor immunity. Upon laser irradiation, OSN generates localized hyperthermia and reactive oxygen species. These effects synergistically enhance oxaliplatin activation and tumor penetration while triggering pyroptosis through dual caspase-1-mediated and caspase-3-dependent pathways. This robust pyroptotic response amplifies the release of damage-associated molecular patterns (e.g., ATP, HMGB1) and pro-inflammatory cytokines (e.g., IL-18, IL-1β), thereby remodeling the immunosuppressive microenvironment, promoting dendritic cell maturation, and facilitating cytotoxic T-cell infiltration. In murine ovarian cancer models, OSN achieved over 90% tumor suppression, significantly outperforming monotherapies. Notably, this nanoplatform establishes long-term immune memory, effectively reducing the risk of tumor relapse. By concurrently targeting immunogenic barriers and metastatic progression through multimodal mechanisms, OSN represents a paradigm-shifting strategy with high clinical translatability for the treatment of aggressive ovarian malignancies.
{"title":"Binary pyroptosis-amplified self-assembling prodrug nanomedicine enhances immunogenicity and inhibits abdominal metastasis in ovarian cancer","authors":"Feng Fang , Min Su , Xue Liu , Jing Chen , Qiwen Liu , Xinran Li , Xuanbo Zhang , Yuanyuan Chen , Huijiao Fu , Zhengchai Chen , Cao Zhou , Xuzi Cai , Zhengfen Li , Zhiqiang Yu , Xuefeng Wang","doi":"10.1016/j.apsb.2025.10.042","DOIUrl":"10.1016/j.apsb.2025.10.042","url":null,"abstract":"<div><div>Ovarian cancer remains a formidable therapeutic challenge due to its high propensity for abdominal metastasis, recurrence, and the presence of an immunosuppressive tumor microenvironment. To overcome these obstacles, we developed a self-assembled nanoplatforms (OSN) by integrating a near-infrared semiconducting polymer with an oxaliplatin(IV) prodrug. This multifunctional design enables a synergistic triple-modality therapy—photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy—within a single nanoparticle, effectively enhancing immunogenic cell death (ICD) and systemic antitumor immunity. Upon laser irradiation, OSN generates localized hyperthermia and reactive oxygen species. These effects synergistically enhance oxaliplatin activation and tumor penetration while triggering pyroptosis through dual caspase-1-mediated and caspase-3-dependent pathways. This robust pyroptotic response amplifies the release of damage-associated molecular patterns (<em>e.g.</em>, ATP, HMGB1) and pro-inflammatory cytokines (<em>e.g.</em>, IL-18, IL-1<em>β</em>), thereby remodeling the immunosuppressive microenvironment, promoting dendritic cell maturation, and facilitating cytotoxic T-cell infiltration. In murine ovarian cancer models, OSN achieved over 90% tumor suppression, significantly outperforming monotherapies. Notably, this nanoplatform establishes long-term immune memory, effectively reducing the risk of tumor relapse. By concurrently targeting immunogenic barriers and metastatic progression through multimodal mechanisms, OSN represents a paradigm-shifting strategy with high clinical translatability for the treatment of aggressive ovarian malignancies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 484-502"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941496","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}
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