Pub Date : 2026-01-01DOI: 10.1016/j.apsb.2025.11.007
Zhenzhen Zhou, Yanying Sun, Da Feng, Zhao Wang, Fabao Zhao, Shenghua Gao, Peng Zhan, Dongwei Kang, Xinyong Liu
HIV-1 reverse transcriptase (RT) is responsible for reverse transcription of viral single-stranded RNA to double-stranded DNA, which plays an important role in the replication cycle of HIV-1 and has been identified as a key target for anti-HIV-1 drug discovery. Among HIV-1 RT inhibitors, allosteric inhibitors acting on non-catalytic sites have the advantages of high efficiency and low cytotoxicity, which are the focus of the research on anti-HIV-1 inhibitors. Great progress has been achieved in the structural biology of HIV-1 RT, which significantly facilitated the development of RT allosteric inhibitors. Herein, we provided a detailed review of the co-crystal structures of small molecule allosteric inhibitors in complex with RT reported in the last decade. Moreover, the strategies to discover novel and efficient inhibitors based on co-crystal structures have also been discussed, expecting to provide a reference for the development of the next-generation anti-HIV-1 drugs.
{"title":"Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design","authors":"Zhenzhen Zhou, Yanying Sun, Da Feng, Zhao Wang, Fabao Zhao, Shenghua Gao, Peng Zhan, Dongwei Kang, Xinyong Liu","doi":"10.1016/j.apsb.2025.11.007","DOIUrl":"10.1016/j.apsb.2025.11.007","url":null,"abstract":"<div><div>HIV-1 reverse transcriptase (RT) is responsible for reverse transcription of viral single-stranded RNA to double-stranded DNA, which plays an important role in the replication cycle of HIV-1 and has been identified as a key target for anti-HIV-1 drug discovery. Among HIV-1 RT inhibitors, allosteric inhibitors acting on non-catalytic sites have the advantages of high efficiency and low cytotoxicity, which are the focus of the research on anti-HIV-1 inhibitors. Great progress has been achieved in the structural biology of HIV-1 RT, which significantly facilitated the development of RT allosteric inhibitors. Herein, we provided a detailed review of the co-crystal structures of small molecule allosteric inhibitors in complex with RT reported in the last decade. Moreover, the strategies to discover novel and efficient inhibitors based on co-crystal structures have also been discussed, expecting to provide a reference for the development of the next-generation anti-HIV-1 drugs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 93-121"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941477","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.2025.10.019
Zheng Sun , Jun Ge , Hui Fu , Ziqiu Chen , Chengcheng Zhao , Xiuyan Li , Yujiao Sun , Zhonggao Gao , Yunfei Li , Yingpeng Li
Conventional drug-delivery systems (DDSs) for oncology often face challenges such as insufficient tumor selectivity, rapid systemic clearance, limited penetration across stromal and immune barriers, and suboptimal biocompatibility. Live immune cell-based drug-delivery systems (LCDDSs) overcome these limitations by exploiting the innate tumor-homing capacity, high biocompatibility, and dynamic tumor microenvironment (TME) interactions intrinsic to leukocytes, facilitating precise targeting with minimal systemic toxicity. Furthermore, immune cells act as “mobile microprocessors”, actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME. Nonetheless, the clinical translation of LCDDSs remains impeded by limited drug-loading capacities, premature payload degradation, potential impairment of immune-cell function, and insufficient persistence in immunosuppressive environments. To overcome these hurdles, immune cell reprogramming via genetic, metabolic, or epigenetic modifications emerges as a promising strategy. Such interventions improve cellular fitness, enhance tumor infiltration, augment payload transport efficiency, confer programmable release profiles, mitigate cellular exhaustion, and increase adaptability to the hostile TME. This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits, drug compatibility considerations, payload loading strategies, and design criteria essential for achieving clinical controllability, safety, and scalability. By integrating immune-cell engineering with cutting-edge drug delivery technologies, reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.
{"title":"Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives","authors":"Zheng Sun , Jun Ge , Hui Fu , Ziqiu Chen , Chengcheng Zhao , Xiuyan Li , Yujiao Sun , Zhonggao Gao , Yunfei Li , Yingpeng Li","doi":"10.1016/j.apsb.2025.10.019","DOIUrl":"10.1016/j.apsb.2025.10.019","url":null,"abstract":"<div><div>Conventional drug-delivery systems (DDSs) for oncology often face challenges such as insufficient tumor selectivity, rapid systemic clearance, limited penetration across stromal and immune barriers, and suboptimal biocompatibility. Live immune cell-based drug-delivery systems (LCDDSs) overcome these limitations by exploiting the innate tumor-homing capacity, high biocompatibility, and dynamic tumor microenvironment (TME) interactions intrinsic to leukocytes, facilitating precise targeting with minimal systemic toxicity. Furthermore, immune cells act as “mobile microprocessors”, actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME. Nonetheless, the clinical translation of LCDDSs remains impeded by limited drug-loading capacities, premature payload degradation, potential impairment of immune-cell function, and insufficient persistence in immunosuppressive environments. To overcome these hurdles, immune cell reprogramming <em>via</em> genetic, metabolic, or epigenetic modifications emerges as a promising strategy. Such interventions improve cellular fitness, enhance tumor infiltration, augment payload transport efficiency, confer programmable release profiles, mitigate cellular exhaustion, and increase adaptability to the hostile TME. This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits, drug compatibility considerations, payload loading strategies, and design criteria essential for achieving clinical controllability, safety, and scalability. By integrating immune-cell engineering with cutting-edge drug delivery technologies, reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 169-197"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941480","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.2025.10.041
Yuhong Gao , Sijia Hua , Xiulin Dong , Kun Zhang , Xiaofeng Zhang , Jianfeng Yang
Vaccines play a crucial role in the prevention and treatment of multiple diseases. Given the constraints of conventional vaccines, the development of nanovaccines, characterized by their superior design flexibility and controllability, has emerged as a compelling alternative. By utilizing nanotechnology, nanovaccines optimize the targeted delivery of antigens and adjuvants, augment antigen presentation, and facilitate precise modulation of immune cell responses, thereby exhibiting substantial potential for both preventive and therapeutic applications across a range of diseases. However, research on nanovaccines is currently stalled at the preclinical stage, with numerous challenges and shortcomings hindering their clinical translation. Herein, we discuss various design concepts and strategies for nanovaccines, along with their biomedical applications, with an emphasis on the challenges, future directions, and strategies of their clinical translation. We specifically highlight the core principles that need to be achieved in the preclinical development of nanovaccines, aiming to explore strategies to overcome existing challenges and promote their clinical application.
{"title":"Concerns and challenges in clinics-guided nanovaccines design and applications","authors":"Yuhong Gao , Sijia Hua , Xiulin Dong , Kun Zhang , Xiaofeng Zhang , Jianfeng Yang","doi":"10.1016/j.apsb.2025.10.041","DOIUrl":"10.1016/j.apsb.2025.10.041","url":null,"abstract":"<div><div>Vaccines play a crucial role in the prevention and treatment of multiple diseases. Given the constraints of conventional vaccines, the development of nanovaccines, characterized by their superior design flexibility and controllability, has emerged as a compelling alternative. By utilizing nanotechnology, nanovaccines optimize the targeted delivery of antigens and adjuvants, augment antigen presentation, and facilitate precise modulation of immune cell responses, thereby exhibiting substantial potential for both preventive and therapeutic applications across a range of diseases. However, research on nanovaccines is currently stalled at the preclinical stage, with numerous challenges and shortcomings hindering their clinical translation. Herein, we discuss various design concepts and strategies for nanovaccines, along with their biomedical applications, with an emphasis on the challenges, future directions, and strategies of their clinical translation. We specifically highlight the core principles that need to be achieved in the preclinical development of nanovaccines, aiming to explore strategies to overcome existing challenges and promote their clinical application.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 198-230"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941481","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.2025.12.022
Olabisi Coker, Jun Yu
{"title":"Commentary on \"Neg-entropy is the true drug target for chronic diseases\"","authors":"Olabisi Coker, Jun Yu","doi":"10.1016/j.apsb.2025.12.022","DOIUrl":"10.1016/j.apsb.2025.12.022","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 656-657"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941469","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.2025.10.018
Yajun Wang , Ming Zhang , Wei Li
The burden imposed by central nervous system disorders (CNSD) on global health is substantial, characterized by a significant impact on quality of life, increased mortality rates, and escalating economic costs. Glial cells, primarily comprising astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs, also known as NG2 cells), play crucial and diverse roles in neurological health and disease. In the treatment of CNSD with traditional herbal medicines, ginseng and its active components have made a notable impression. This comprehensive review investigates the interaction between ginseng and these essential glial cells, detailing their contributions to neurological well-being and disease states. Additionally, it thoroughly assesses the effects of ginseng on glial function, highlighting its neuroprotective potential through anti-inflammatory, antioxidative, and other restorative actions via complex molecular pathways. Moreover, the review analyzes how ginseng can facilitate neuronal viability and regeneration, as well as modulate signaling cascades, thereby highlighting the therapeutic potential of ginseng in the management of CNSD.
{"title":"Targeting glial cells: Unveiling the neuroprotective mechanisms of Ginseng in the brain microenvironment","authors":"Yajun Wang , Ming Zhang , Wei Li","doi":"10.1016/j.apsb.2025.10.018","DOIUrl":"10.1016/j.apsb.2025.10.018","url":null,"abstract":"<div><div>The burden imposed by central nervous system disorders (CNSD) on global health is substantial, characterized by a significant impact on quality of life, increased mortality rates, and escalating economic costs. Glial cells, primarily comprising astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs, also known as NG2 cells), play crucial and diverse roles in neurological health and disease. In the treatment of CNSD with traditional herbal medicines, ginseng and its active components have made a notable impression. This comprehensive review investigates the interaction between ginseng and these essential glial cells, detailing their contributions to neurological well-being and disease states. Additionally, it thoroughly assesses the effects of ginseng on glial function, highlighting its neuroprotective potential through anti-inflammatory, antioxidative, and other restorative actions <em>via</em> complex molecular pathways. Moreover, the review analyzes how ginseng can facilitate neuronal viability and regeneration, as well as modulate signaling cascades, thereby highlighting the therapeutic potential of ginseng in the management of CNSD.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 13-34"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941474","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.2025.11.016
Wenting Wang , Yanfei Liu , Yiwen Li , Qian Xu , Mengmeng Zhu , Jing Cui , Yue Liu
Vascular calcification (VC) is a marker of substantial vascular damage in patients with diabetes and has been recognized as a predictor of cardiovascular events and all-cause mortality. To date, no effective therapeutic strategy has been formulated for the management of VC. In this study, we integrated the treatment regimen of the Danlian-Tongmai (DLTM) formula, a traditional Chinese medicine (TCM) with anti-diabetic VC (anti-DVC) effects with intermittent fasting (IF), and established the Chinese medicine and intermittent fasting integration therapy (CMIT). CMIT synergistically enhanced the regulation of calcium-phosphorus homeostasis and vascular repair, and demonstrated significantly greater efficacy than DLTM or IF monotherapy in inhibiting calcium deposition and osteogenic differentiation both in vivo and in vitro. Transcriptomic sequencing revealed that the miR21-5p/Tpm1 axis mediated the anti-calcification effect of CMIT. MiR21-5p promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating Tpm1, while CMIT inhibited such processes. In conclusion, this study demonstrated that CMIT inhibited the osteogenic differentiation of VSMC and restored its contractile phenotype by inhibiting the activation of the miR21-5p/Tpm1 axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.
{"title":"Chinese medicine and intermittent fasting integration therapy attenuate diabetic vascular calcification via miR21-5p/Tpm1-mediated osteogenic differentiation of VSMCs","authors":"Wenting Wang , Yanfei Liu , Yiwen Li , Qian Xu , Mengmeng Zhu , Jing Cui , Yue Liu","doi":"10.1016/j.apsb.2025.11.016","DOIUrl":"10.1016/j.apsb.2025.11.016","url":null,"abstract":"<div><div>Vascular calcification (VC) is a marker of substantial vascular damage in patients with diabetes and has been recognized as a predictor of cardiovascular events and all-cause mortality. To date, no effective therapeutic strategy has been formulated for the management of VC. In this study, we integrated the treatment regimen of the Danlian-Tongmai (DLTM) formula, a traditional Chinese medicine (TCM) with anti-diabetic VC (anti-DVC) effects with intermittent fasting (IF), and established the Chinese medicine and intermittent fasting integration therapy (CMIT). CMIT synergistically enhanced the regulation of calcium-phosphorus homeostasis and vascular repair, and demonstrated significantly greater efficacy than DLTM or IF monotherapy in inhibiting calcium deposition and osteogenic differentiation both <em>in vivo</em> and <em>in vitro</em>. Transcriptomic sequencing revealed that the <em>miR21-5p</em>/<em>Tpm1</em> axis mediated the anti-calcification effect of CMIT. <em>MiR21-5p</em> promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating <em>Tpm1</em>, while CMIT inhibited such processes. In conclusion, this study demonstrated that CMIT inhibited the osteogenic differentiation of VSMC and restored its contractile phenotype by inhibiting the activation of the <em>miR21-5p</em>/<em>Tpm1</em> axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 352-370"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941527","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}
Osteoarthritis (OA) presents significant therapeutic challenges due to the irreversible cartilage loss driven by chondrocyte metabolic imbalance and a severe inflammatory microenvironment. Conventional treatments are limited by poor chondrocyte-targeting and ineffectiveness of single-target medication. Here, we develop an anti-inflammatory neutrophil-derived microvesicle (MV)-based gene therapy for OA treatment, which leverages the intrinsic cartilage-penetrating capabilities of MVs to improve the targeted delivery of microRNA-140-5p (miR140) to chondrocytes, and the synergistic effect of anti-inflammatory MVs and miR140 to dual modulate the metabolic homeostasis of chondrocytes and the inflamed microenvironment. We demonstrate that miR140@MVs not only alleviate synovial inflammation via reprogramming the phenotypes of macrophages and adsorbing inflammatory factors, but also restore normal cartilage thickness in a destabilized medial meniscus mouse model due to the rebuilt metabolic homeostasis of chondrocytes, thus gaining a remarkable therapeutic effect up to 28 days. This study provides an immuno-stimulation method for production of anti-inflammatory MVs, and puts forward a safe and effective MVs-based miRNA system for treatment of joint-related diseases.
{"title":"Dual metabolic-inflammation modulation in MicroRNA@neutrophil-derived microvesicles achieve robust osteoarthritis therapy","authors":"Yijun Chen, Yongbin Wang, Ruonan Yan, Yichen Liu, Yupeng Dai, Lingjing Xue, Caoyun Ju, Can Zhang","doi":"10.1016/j.apsb.2025.09.020","DOIUrl":"10.1016/j.apsb.2025.09.020","url":null,"abstract":"<div><div>Osteoarthritis (OA) presents significant therapeutic challenges due to the irreversible cartilage loss driven by chondrocyte metabolic imbalance and a severe inflammatory microenvironment. Conventional treatments are limited by poor chondrocyte-targeting and ineffectiveness of single-target medication. Here, we develop an anti-inflammatory neutrophil-derived microvesicle (MV)-based gene therapy for OA treatment, which leverages the intrinsic cartilage-penetrating capabilities of MVs to improve the targeted delivery of microRNA-140-5p (miR140) to chondrocytes, and the synergistic effect of anti-inflammatory MVs and miR140 to dual modulate the metabolic homeostasis of chondrocytes and the inflamed microenvironment. We demonstrate that miR140@MVs not only alleviate synovial inflammation <em>via</em> reprogramming the phenotypes of macrophages and adsorbing inflammatory factors, but also restore normal cartilage thickness in a destabilized medial meniscus mouse model due to the rebuilt metabolic homeostasis of chondrocytes, thus gaining a remarkable therapeutic effect up to 28 days. This study provides an immuno-stimulation method for production of anti-inflammatory MVs, and puts forward a safe and effective MVs-based miRNA system for treatment of joint-related diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 423-443"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941531","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.2025.08.019
Aihua Jin , Nuoya Wang , Yanhong Liu , Shuangqing Wang , Liqing Chen , Liming Gong , Wei Huang , Zhonggao Gao , Mingji Jin
Due to the invasive growth of glioblastomas (GBM) and their resistance to conventional chemotherapy, the efficacy of GBM treatment remains limited. Biomimetic BBB-penetrating hybrid nanovehicles, engineered through homologous cell membrane fusion between cancer cells and protein corona (PC)-mediated liposomes coated with cancer cell membranes, have been explored for brain-targeted drug delivery. In this study, T10 peptide-modified cell membrane-coated liposomes were used to construct an in situ transferrin (Tf) PC-mediated lipo-complex carrying a respiratory depressant agent (metformin, MET) and a photosensitizer (Chlorin, Ce6), creating a transferrin- and cancer cell-targeting delivery system (MET/Ce6@Lipo@CM@T10). MET/Ce6@Lipo@CM@T10 possesses a spherical core–shell structure with uniform distribution while maintaining low systemic toxicity. Upon irradiation, MET/Ce6@Lipo@CM@T10 effectively inhibited cell proliferation and induced apoptosis via photodynamic therapy (PDT). Simultaneously, the loaded MET alleviated intracellular hypoxia caused by PDT, thereby enhancing anti-tumor efficacy. The establishment of an in vitro BBB model and 3D tumor spheroid experiments confirmed that MET/Ce6@Lipo@CM@T10 effectively crossed BBB and deeply accumulated within tumor tissues. As a result, in in vivo animal experiments, MET/Ce6@Lipo@CM@T10 significantly inhibited tumor growth, promoted tumor necrosis and apoptosis, and demonstrated systemic safety. In conclusion, MET/Ce6@Lipo@CM@T10 demonstrated enhanced PDT effects on GBM, and will provide new insights and methods for GBM treatment.
{"title":"Endogenic transferrin-targeted cell membrane-coated biomimetic lipo-complexes for efficient targeting and enhanced antitumor efficacy in orthotopic glioblastoma","authors":"Aihua Jin , Nuoya Wang , Yanhong Liu , Shuangqing Wang , Liqing Chen , Liming Gong , Wei Huang , Zhonggao Gao , Mingji Jin","doi":"10.1016/j.apsb.2025.08.019","DOIUrl":"10.1016/j.apsb.2025.08.019","url":null,"abstract":"<div><div>Due to the invasive growth of glioblastomas (GBM) and their resistance to conventional chemotherapy, the efficacy of GBM treatment remains limited. Biomimetic BBB-penetrating hybrid nanovehicles, engineered through homologous cell membrane fusion between cancer cells and protein corona (PC)-mediated liposomes coated with cancer cell membranes, have been explored for brain-targeted drug delivery. In this study, T<sub>10</sub> peptide-modified cell membrane-coated liposomes were used to construct an <em>in situ</em> transferrin (Tf) PC-mediated lipo-complex carrying a respiratory depressant agent (metformin, MET) and a photosensitizer (Chlorin, Ce6), creating a transferrin- and cancer cell-targeting delivery system (MET/Ce6@Lipo@CM@T<sub>10</sub>). MET/Ce6@Lipo@CM@T<sub>10</sub> possesses a spherical core–shell structure with uniform distribution while maintaining low systemic toxicity. Upon irradiation, MET/Ce6@Lipo@CM@T<sub>10</sub> effectively inhibited cell proliferation and induced apoptosis <em>via</em> photodynamic therapy (PDT). Simultaneously, the loaded MET alleviated intracellular hypoxia caused by PDT, thereby enhancing anti-tumor efficacy. The establishment of an <em>in vitro</em> BBB model and 3D tumor spheroid experiments confirmed that MET/Ce6@Lipo@CM@T<sub>10</sub> effectively crossed BBB and deeply accumulated within tumor tissues. As a result, in <em>in vivo</em> animal experiments, MET/Ce6@Lipo@CM@T<sub>10</sub> significantly inhibited tumor growth, promoted tumor necrosis and apoptosis, and demonstrated systemic safety. In conclusion, MET/Ce6@Lipo@CM@T<sub>10</sub> demonstrated enhanced PDT effects on GBM, and will provide new insights and methods for GBM treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 574-595"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941500","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.2025.09.025
Minju Han , Eunji Kim , Minchan Jeong , Solbi Kim , Hyo-Jin Lee , Heung Jin Jeon
The tumor microenvironment is characterized by an immunosuppressive state. Although PD-1/PD-L1 blockade therapy activates the immune system against tumors, it has limited long-term efficacy, prompting the development of combination therapies with targeted treatments to improve cancer treatment outcomes. Recent advancements have revitalized interest in using attenuated Salmonella strains as cancer therapeutics that target tumors, induce immune responses, and promote tumor cell death, although complete tumor suppression remains challenging. We aimed to induce antitumor effects by activating the suppressed immune system within the tumor microenvironment using Salmonella-mediated secretion of interleukin-21 (IL-21). We used the tumor-targeting ability of Salmonella and its flagellar type-3 secretion system (FT3SS) to induce the secretion of IL-21 into the tumor microenvironment via the flagellar system and evaluated the local immune response. We also evaluated the efficacy of combining Salmonella-mediated IL-21 delivery and anti-PD-L1 therapy in a mouse model. IL-21 secretion promoted the recruitment of CD4+ and CD8+ T cells and enhanced the expression of cytotoxicity-related molecules. Tumor-bearing mice treated with the combination therapy with anti-PD-L1 antibodies showed improved survival rates and enhanced tumor growth inhibition. This study demonstrates the tumor-targeting capability and in vivo safety of Salmonella, highlighting its potential as a powerful cancer therapy platform.
{"title":"Attenuated Salmonella secreting interleukin-21 activates T-cells and induces anti-tumor effects","authors":"Minju Han , Eunji Kim , Minchan Jeong , Solbi Kim , Hyo-Jin Lee , Heung Jin Jeon","doi":"10.1016/j.apsb.2025.09.025","DOIUrl":"10.1016/j.apsb.2025.09.025","url":null,"abstract":"<div><div>The tumor microenvironment is characterized by an immunosuppressive state. Although PD-1/PD-L1 blockade therapy activates the immune system against tumors, it has limited long-term efficacy, prompting the development of combination therapies with targeted treatments to improve cancer treatment outcomes. Recent advancements have revitalized interest in using attenuated <em>Salmonella</em> strains as cancer therapeutics that target tumors, induce immune responses, and promote tumor cell death, although complete tumor suppression remains challenging. We aimed to induce antitumor effects by activating the suppressed immune system within the tumor microenvironment using <em>Salmonella</em>-mediated secretion of interleukin-21 (IL-21). We used the tumor-targeting ability of <em>Salmonella</em> and its flagellar type-3 secretion system (FT3SS) to induce the secretion of IL-21 into the tumor microenvironment <em>via</em> the flagellar system and evaluated the local immune response. We also evaluated the efficacy of combining <em>Salmonella</em>-mediated IL-21 delivery and anti-PD-L1 therapy in a mouse model. IL-21 secretion promoted the recruitment of CD4<sup>+</sup> and CD8<sup>+</sup> T cells and enhanced the expression of cytotoxicity-related molecules. Tumor-bearing mice treated with the combination therapy with anti-PD-L1 antibodies showed improved survival rates and enhanced tumor growth inhibition. This study demonstrates the tumor-targeting capability and <em>in vivo</em> safety of <em>Salmonella</em>, highlighting its potential as a powerful cancer therapy platform.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 239-251"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941390","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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