Biomedicine & Pharmacotherapy最新文献

{"title":"Visnagin mitigates acute kidney injury caused by lipopolysaccharide administration by inhibiting the NF-κB and pyroptosis pathways","authors":"Sheng-Wen Wu ,&nbsp;Chien-Ying Lee ,&nbsp;Shiuan-Shinn Lee ,&nbsp;Wen-Ying Chen ,&nbsp;Chun-Jung Chen ,&nbsp;Ching-Chi Tseng ,&nbsp;Chen-Yu Chiang ,&nbsp;Yu-Hsiang Kuan","doi":"10.1016/j.biopha.2025.118578","DOIUrl":"10.1016/j.biopha.2025.118578","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Sepsis-associated acute kidney injury (AKI) is a life-threatening complication marked by inflammation-driven renal dysfunction. Although advances have been made in supportive care, pharmacologic therapies targeting the underlying molecular mechanisms of sepsis-associated AKI are lacking. Visnagin, a furanochromone derivative with anti-inflammatory properties, has yet to be explored in treatment for sepsis-associated AKI.</div></div><div><h3>Experimental approach</h3><div>This study used a network pharmacology approach to identify visnagin targets associated with AKI. We conducted gene enrichment and protein-protein interaction analyses and performed molecular docking to predict binding affinities between visnagin and key inflammatory proteins. An in vivo murine model of LPS-induced AKI was established to evaluate the protection of visnagin. Renal function was assessed through serum creatinine and blood urea nitrogen levels. Additionally, histological injury, inflammatory cytokine expression, and molecular pathways were analysed.</div></div><div><h3>Key results</h3><div>Bioinformatics analyses identified MAPK1, MAPK14, NFKB1, and CASP1 as hub genes potentially targeted by visnagin. Molecular docking confirmed strong binding affinities between visnagin and these proteins that exceeded the binding affinity of dexamethasone in key inflammatory targets. In vivo, visnagin substantially reduced LPS-induced renal dysfunction and histopathological damage in a dose-dependent manner. Visnagin suppressed the phosphorylation of p38 MAPK and extracellular signal-related kinase, decreased NF-κB activation, and inhibited the generation of proinflammatory cytokines. Moreover, visnagin attenuated pyroptosis by inhibiting the NLRP3/apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain/caspase-1/Gasdermin-D axis.</div></div><div><h3>Conclusion and implications</h3><div>Visnagin mitigates LPS-induced AKI by targeting multiple signalling pathways, particularly NF-κB-mediated inflammation and NLRP3 inflammasome-mediated pyroptosis. These findings suggest that visnagin is a promising multitarget candidate for treating sepsis-associated AKI.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118578"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteasome-mediated ubiquitination in neural regeneration","authors":"Huanyi Li ,&nbsp;Yiwen Hu ,&nbsp;Meili Cheng ,&nbsp;Jialin Wang ,&nbsp;Mingxia Zhao ,&nbsp;Bolun Cao ,&nbsp;Yulu Zhao ,&nbsp;Jingjing Jiang","doi":"10.1016/j.biopha.2025.118563","DOIUrl":"10.1016/j.biopha.2025.118563","url":null,"abstract":"<div><div>The proteasome, the principal intracellular protein-degradation system, is essential for nerve regeneration after injury.This review summarizes recent evidence that the proteasome orchestrates axonal regeneration by modulating growth-cone formation, microtubule dynamics, reactive oxygen species (ROS) levels, and neuroinflammation. Proteasomes are delivered to growth cones via retrograde axonal transport, and their localization and activity depend on neuronal maturation and axon length.They further promote growth-cone assembly and axonal extension by regulating tubulin expression and polymerization.As key signaling molecules, ROS levels are tightly coupled to proteasome activity; their reciprocal interactions fine-tune axonal regrowth. Notably, immunoproteasome subunits such as PSMB5i contribute to neurodegeneration via inflammatory pathways. In a cohort of 316 ischemic stroke patients, plasma levels of LMP2, MECL-1, and LMP7 were markedly elevated in the 13.3 % who developed hemorrhagic transformation (P &lt; 0.05), suggesting their utility as early biomarkers of stroke complications. Elucidating these proteasome-driven mechanisms in both regeneration and pathology will inform novel therapeutic strategies for neural repair and related disorders.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118563"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision targeting of CXCR4+ leukemia cells by a humanized MMAE-nanoconjugate in an AML mouse model","authors":"Annabel Garcia-León ,&nbsp;Julián I. Mendoza ,&nbsp;Ariana Rueda ,&nbsp;Lorena Alba-Castellon ,&nbsp;Josep F. Nomdedéu ,&nbsp;Alberto Gallardo ,&nbsp;Jorge Sierra ,&nbsp;Ana Garrido ,&nbsp;Esther Vázquez ,&nbsp;Antonio Villaverde ,&nbsp;Ramon Mangues ,&nbsp;Ugutz Unzueta ,&nbsp;Isolda Casanova","doi":"10.1016/j.biopha.2025.118573","DOIUrl":"10.1016/j.biopha.2025.118573","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) presents major clinical challenges due to chemoresistance and high relapse rates, primarily driven by therapy-resistant leukemic stem cells (LSCs) within the bone marrow. To address this issue, we developed T22-HSNBT-H6-MMAE, a novel humanized nanoconjugate designed to target CXCR4^⁺ cells while delivering the cytotoxic payload monomethyl auristatin E (MMAE). CXCR4 signaling pathway plays a critical role in LSC survival by preserving stem-like properties and activating protective mechanisms that promote treatment resistance. Moreover, CXCR4 is overexpressed in approximately 50 % of AML patients and is associated with poor prognosis and high relapse rates. We evaluated the therapeutic potential of T22-HSNBT-H6-MMAE using <em>in vitro</em> assays with AML cell lines and primary patient samples, as well as <em>in vivo</em> studies in a disseminated AML mouse model. Our results demonstrated that T22-HSNBT-H6-MMAE exerts a CXCR4-dependent cytotoxic effect through mitotic catastrophe and apoptosis induction in CXCR4^⁺ AML cell lines. <em>In vivo</em> evaluation in a disseminated CXCR4^⁺ AML mouse model showed potent antineoplastic activity, with complete suppression of leukemic dissemination and significantly prolonged survival, all without systemic toxicity. Notably, the nanoconjugate remained effective even in models with extensive bone marrow involvement and exhibited activity against diverse patient-derived CXCR4^⁺ AML blasts, while sparing healthy donor bone marrow and peripheral blood mononuclear cells (PBMCs) from significant toxicity. Collectively, these findings highlight T22-HSNBT-H6-MMAE as a promising therapeutic candidate for a broad range of AML patients, offering selective antineoplastic activity against CXCR4^⁺ leukemic cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118573"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging predictions with experimental reality: In vitro evaluation of phenolic natural products as SARS-CoV-2 exoribonuclease inhibitors","authors":"Matěj Danda ,&nbsp;Barbora Chvátalová ,&nbsp;Daniela Nečasová ,&nbsp;Ivana Křížová ,&nbsp;Tomáš Ruml ,&nbsp;Michaela Rumlová","doi":"10.1016/j.biopha.2025.118588","DOIUrl":"10.1016/j.biopha.2025.118588","url":null,"abstract":"<div><div>SARS-CoV-2 exoribonuclease (ExoN) is essential for viral replication, contributing to proofreading, RNA synthesis, and genomic RNA recombination. As such, it represents a promising target for antiviral drugs. Several low-molecular-weight inhibitors, including disulfiram and aurintricarboxylic acid (ATA), have been reported to inhibit ExoN activity. Computational studies have also suggested that various natural phenolic compounds may inhibit ExoN; however, their inhibitory potency remains largely unknown. In this study, we systematically evaluated the inhibitory potency of 60 phenolic phytochemicals, including flavonoids, phenolic acids, coumarins, and other related compounds, using a dual-assay approach, with ATA as the reference inhibitor. Initially, we used nano-differential scanning fluorimetry to assess the thermal stabilization or destabilization of the enzyme induced by compound binding. Subsequently, we performed a TBE-PAGE-based enzymatic activity assay to examine ExoN activity inhibition. Selected compounds were then validated using a FRET-based enzymatic assay. While none of the compounds achieved the ATA’s inhibitory efficacy, three compounds demonstrated measurable inhibitory activity: myricetin (IC₅₀ = 142 µM), ellagic acid (IC₅₀ = 44.4 µM), and shikonin (IC₅₀ = 7.92 µM). Our dual assay approach, complemented by crosslinking experiments, revealed that shikonin exhibits a distinct inhibitory mechanism, possibly involving the disruption of ExoN subunit interactions. These findings emphasize the necessity of experimental validation following <em>in silico</em> screening, particularly for promiscuous chemicals such as phenolic natural products. This approach may help to narrow down rationally designed compounds for further optimization.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118588"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances and clinical potential of hyaluronic acid methacrylate (HAMA)/ceramic composites in oral and dental regenerative therapies: A comprehensive review","authors":"Mohammad Golrokhian ,&nbsp;Haleh Fakhimi Rezaei ,&nbsp;Maryam Rezaeianjam ,&nbsp;Bita Moslem ,&nbsp;Kimia Naderpour ,&nbsp;Amir Abbas Seraji","doi":"10.1016/j.biopha.2025.118590","DOIUrl":"10.1016/j.biopha.2025.118590","url":null,"abstract":"<div><div>Hyaluronic acid methacrylate (HAMA) has emerged as a promising biomaterial for oral and dental applications due to its inherent biocompatibility, controllable biodegradability, and tunable mechanical properties. The incorporation of ceramic components (e.g., hydroxyapatite, tricalcium phosphate, bioactive glass) into HAMA-based composites synergistically enhances their mechanical robustness, bioactivity, and osteogenic capacity, thereby expanding their utility in dental tissue engineering, periodontal regeneration, and implant surface functionalization. This review provides a comprehensive analysis of recent advancements in the design, fabrication, and application of HAMA/ceramic composites. Our analysis of the literature reveals that these composites demonstrate significant promise: they enhance compressive modulus, support high cell viability in 3D-bioprinted constructs, and achieve sustained release of antimicrobials and ions to concurrently combat infection and promote osteogenesis. Key findings indicate their efficacy in guided bone regeneration, periodontal defect repair, where they reduce inflammatory markers and inhibit periodontal pathogens, and as bioactive implant coatings that improve osseointegration. Despite these advancements, significant challenges persist in scalability, long-term structural stability, and clinical translation. By integrating insights from materials science, cellular biology, and clinical dentistry, this review concludes that HAMA/ceramic composites represent a paradigm-shifting platform for next-generation dental therapies. Their unique combination of properties positions them to overcome the limitations of conventional biomaterials, though future efforts must focus on standardizing fabrication protocols and validating their efficacy in controlled human trials.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118590"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in bioconjugation: From strategies to design and clinical applications","authors":"Faezeh Samieipour ,&nbsp;Hassan Dianat-Moghadam ,&nbsp;Hossein Khanahmad","doi":"10.1016/j.biopha.2025.118593","DOIUrl":"10.1016/j.biopha.2025.118593","url":null,"abstract":"<div><div>Bioconjugation is defined as the covalent attachment of biomolecules, such as proteins, carbohydrates, nucleic acids, or lipids, to another biomolecule or functional entity such as synthetic polymers, fluorescent probes, drugs, dyes, and targeting ligands. Bioconjugation plays a key role in modern biotechnology and medicine, enabling precise control over molecular recognition, stability, and biodistribution. This review provides a comprehensive and integrative perspective on bioconjugation, encompassing both traditional and emerging strategies while critically comparing their efficiency, stability, and clinical applicability. It evaluates the strengths and limitations of various approaches, from classical amide and thiol couplings to advanced bioorthogonal click chemistry. Furthermore, the review highlights innovative directions in optimizing bioconjugation, including linker design, enhanced stability profiles, stimuli-responsive release mechanisms, and predictive release kinetics. The work integrates recent advances into a framework that addresses key challenges, such as site-specificity, immunogenicity, and scalability and offers a practical guide for next-generation diagnostics and therapeutics.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118593"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine N-Oxide (TMAO) and cancer risk: Insights into a possible link","authors":"Biki Saha ,&nbsp;Antara Banerjee ,&nbsp;Rupak Pathak ,&nbsp;Asim K. Duttaroy ,&nbsp;Surajit Pathak","doi":"10.1016/j.biopha.2025.118592","DOIUrl":"10.1016/j.biopha.2025.118592","url":null,"abstract":"<div><div>The gut microbiota play a crucial role in cancer pathogenesis, partly through metabolites derived from dietary components or host compounds. Among these, trimethylamine N-oxide (TMAO), a secondary gut microbiota-derived metabolite has gained attention for its potential link to cancer. TMAO is formed when gut microbes convert dietary choline, carnitine, and betaine into trimethylamine (TMA), which is then oxidized in the liver by FMO3. While TMAO has been well studied in cardiovascular, kidney, and metabolic diseases, growing evidence links elevated TMAO levels to increased risks of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Although the exact mechanisms remain unclear, TMAO appears to contribute to cancer progression by promoting inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance. This review discusses the dietary and microbial pathways involved in TMAO synthesis, its role in cancer progression, and critically evaluates the current literature on its potential contribution to cancer. Understanding the role of TMAO could offer new strategies for cancer prevention and therapy that target the gut microbiota and their metabolites.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118592"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes in Alzheimer’s disease: From pathogenesis to therapeutics—A comprehensive review of diagnostic and drug delivery applications","authors":"Mona Shahlaei ,&nbsp;Hamed Afkhami ,&nbsp;Amirhossein Ahmadieh-Yazdi ,&nbsp;Seyed Hashem Mirmazloumi ,&nbsp;Seyedeh Saeideh Sahraei ,&nbsp;Mohammad Akbari ,&nbsp;Piao Yang ,&nbsp;Hamed Manoochehri ,&nbsp;Hamid Tanzadehpanah ,&nbsp;Hanie Mahaki ,&nbsp;Aravind Sundararaman ,&nbsp;Sreedivya Mohan ,&nbsp;Mohsen Sheykhhasan ,&nbsp;Sharafaldin Al-Musawi ,&nbsp;Paola Dama","doi":"10.1016/j.biopha.2025.118548","DOIUrl":"10.1016/j.biopha.2025.118548","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is still a major unmet medical challenge, with limited treatment options and a critical need for early diagnostics. Exosomes, nanoscale extracellular vesicles with a lipid bilayer, are pivotal players in intercellular communication and promising tools for AD management. Their unique ability to cross the blood<img>brain barrier, low immunogenicity, and ability for cargo delivery make them ideal candidates for targeted drug delivery. This review comprehensively examines the biology of exosomes—including their structure, biogenesis, release, and uptake—and evaluates advanced methods for their isolation, purification, and characterization. We highlight their dual role in AD pathogenesis, where they can propagate pathological proteins such as amyloid-β and tau, and in therapeutic applications, where engineered exosomes deliver neuroprotective agents. Furthermore, exosomal biomarkers in biofluids show significant potential for noninvasive early diagnosis. Recent advances in loading strategies and surface engineering have been discussed, alongside challenges in scalability and safety. This synthesis bridges current knowledge with future directions, emphasizing the translational potential of exosomes in AD therapeutics and diagnostics.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118548"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of immune cell therapeutics targeting α-PD-L1 in lung cancer","authors":"A.-Ram Lee ,&nbsp;Hee Young Kang ,&nbsp;Yu Bin Lee ,&nbsp;Soo Yun Lee ,&nbsp;Min-Heui Yoo ,&nbsp;Seok-Min Kim ,&nbsp;Wan-Jung Im ,&nbsp;Ji-Young Kim ,&nbsp;Kyoung-Sik Moon ,&nbsp;Tae-Don Kim ,&nbsp;Sang-Jin Park","doi":"10.1016/j.biopha.2025.118594","DOIUrl":"10.1016/j.biopha.2025.118594","url":null,"abstract":"<div><div>Autologous chimeric antigen receptor (CAR)-T therapies have shown exceptional efficacy against hematological malignancies and potential against various diseases. However, robust in vitro efficacy and safety tests (ESTs), crucial for their clinical application, are lacking. Here, we developed α-PD-L1- natural killer (NK) cells by engineering NK92 cells to express a CAR targeting PD-L1, and selected three lead CAR-NK cell lines. Using an in vitro EST that integrates direct/indirect cytotoxicity and soft agar formation assays, we identified a candidate CAR-NK cell line (α-PD-L1-#2L5-NK). To validate the EST, we assessed the in vivo efficacy of α-PD-L1-#2L5-NK in a murine xenograft model, demonstrating significant tumor size and weight reduction. Additionally, α-PD-L1-#2L5-NK did not induce mortality or toxic effects in mice. Overall, this EST is valuable for screening and identifying safe and effective cell therapies in the off-the-shelf immune cell therapy field. It can help reduce the likelihood of failures of therapeutics and establish standards for quality control and regulatory aspects.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118594"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fighting cancer smarter: Using hydrogel delivery systems to target chemokines","authors":"Hossein Khorramdelazad ,&nbsp;Pegah Yaraghi ,&nbsp;Zahra Shirzad ,&nbsp;Armin Boroumand ,&nbsp;Reyhaneh Arfaei ,&nbsp;Abbas Kheyri ,&nbsp;Mohammad Keshavarz ,&nbsp;Fatemeh Daj ,&nbsp;Maryam Keykhaee","doi":"10.1016/j.biopha.2025.118601","DOIUrl":"10.1016/j.biopha.2025.118601","url":null,"abstract":"<div><div>Chemokines organize immune cell locomotion and trafficking in the tumor milieu, exerting dual roles by either boosting antitumor immunity (e.g., CXCL9/10/11 recruit effector T-cells) or promoting tumor progression (e.g., CCL2 supports immunosuppressive myeloid cells). Short half-lives, off-target effects, and tumor microenvironment (TME) barriers such as hypoxia and acidity hinder systemic administration of chemokines. Hydrogel-based delivery systems provide a biocompatible and tunable platform for controlled, localized chemokine release, thereby improving cargo stability and facilitating effector T-cell infiltration. Preclinical evidence also suggests that hydrogel-delivered chemokines may enhance responses to immune checkpoint inhibitors (ICIs), offering improved tumor regression compared to ICIs alone. Importantly, this review addresses not only therapeutic potential but also safety considerations, including local tissue toxicity, immune overstimulation, and translational challenges. Collectively, the article synthesizes chemokine biology, hydrogel-based chemokine delivery strategies, and preclinical outcomes, while outlining key hurdles and future directions for optimizing chemokine-focused cancer immunotherapy. However, clinical evidence remains limited, underscoring the need for close monitoring of immune-related adverse events (irAEs) and long-term effects on immune homeostasis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118601"},"PeriodicalIF":7.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}