Biomaterials最新文献

{"title":"Optimal structural characteristics of osteoinductivity in bioceramics derived from a novel high-throughput screening plus machine learning approach","authors":"Yunyi Liu ,&nbsp;Quanle Cao ,&nbsp;Shengyi Yong ,&nbsp;Jing Wang ,&nbsp;Xuening Chen ,&nbsp;Yumei Xiao ,&nbsp;Jiangli Lin ,&nbsp;Mingli Yang ,&nbsp;Kefeng Wang ,&nbsp;Xiangfeng Li ,&nbsp;Xiangdong Zhu ,&nbsp;Xingdong Zhang","doi":"10.1016/j.biomaterials.2025.123348","DOIUrl":"10.1016/j.biomaterials.2025.123348","url":null,"abstract":"<div><div>Osteoinduction is an important feature of the next generation of bone repair materials. But the key structural factors and parameters of osteoinductive scaffolds are not yet clarified. This study leverages the efficiency of high-throughput screening in identifying key structural factors, performs screening of 24 different porous structures using 3D printed calcium phosphate (CaP) ceramic scaffolds. Based on <em>in vitro</em> and <em>in vivo</em> evaluations, along with machine learning and nonlinear fitting, it explores the complex relationship between osteoinductive properties and scaffold configurations. Results indicate that bone regenerative ability is largely affected by porosity and specific surface area (SSA), while pore geometry has a negligible effect. The optimal structural parameters were identified as a porous structure with SSA of 10.49–10.69 mm² mm⁻³ and permeability of 3.74 × 10⁻⁹ m², which enhances osteoinductivity and scaffold properties, corresponding to approximately 65 %–70 % porosity. Moreover, nonlinear fitting reveals specific correlations among SSA, permeability and osteogenic gene expressions. We established a data-driven high-throughput screening methodology and proposed a parametric benchmark for osteoinductive structures, providing critical insights for the design of future osteoinductive scaffolds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123348"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3","authors":"Nana Meng ,&nbsp;Jiasheng Lu ,&nbsp;Jianfen Zhou ,&nbsp;Shengmin Yang ,&nbsp;Chen Zhang ,&nbsp;Ruiyi Jia ,&nbsp;Yuan Ding ,&nbsp;Yanning Bao ,&nbsp;Jun Wang ,&nbsp;Xiaopei Ma ,&nbsp;Ruohan Chen ,&nbsp;Zhixuan Jiang ,&nbsp;Cao Xie ,&nbsp;Linwei Lu ,&nbsp;Weiyue Lu","doi":"10.1016/j.biomaterials.2025.123350","DOIUrl":"10.1016/j.biomaterials.2025.123350","url":null,"abstract":"<div><div>One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin <em>α</em>_<em>v</em><em>β</em>_<em>3</em>. Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the <em>in vivo</em> immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123350"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow adipocytes in cancer: Mechanisms, models, and therapeutic implications","authors":"Agathe Bessot ,&nbsp;Jennifer Gunter ,&nbsp;Jacqui McGovern ,&nbsp;Nathalie Bock","doi":"10.1016/j.biomaterials.2025.123341","DOIUrl":"10.1016/j.biomaterials.2025.123341","url":null,"abstract":"<div><div>Adipose tissue is the primary site of energy storage in the body and a key regulator of metabolism. However, different adipose depots exhibit distinct molecular and phenotypic characteristics that have yet to be fully unraveled. While initially considered inert, bone marrow adipocytes (BMAs) have been recognized as key regulators of bone homeostasis, and more recently bone pathologies, although many unknowns remain. In this review, we summarize the current knowledge on BMAs, focusing on their distinct characteristics, functional significance in bone physiology and metabolism, as well as their emerging role in cancer pathogenesis. We present and discuss the current methodologies for investigating BMA-cancer interactions, encompassing both <em>in vitro</em> 3D culture systems and <em>in vivo</em> models, and their limitations in accurately replicating the phenotypes and biological processes of the human species. We highlight the imperative for advancing towards humanized models to better mimic the complexities of human physiology and disease progression. Finally, therapeutic strategies targeting metabolism or BMA-secreted factors, such as anti-cholesterol drugs, hold considerable promise in cancer treatment. We present the synergistic avenue of combining conventional cancer therapies with agents targeting adipocyte signaling to amplify treatment efficacy. Developing preclinical models that more faithfully replicate human pathological and physiological processes will lead to more accurate mechanistic understanding of the role of BMAs in bone metastasis and lead to more relevant preclinical drug screening.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123341"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative sarcoma therapy using multifaceted nano-PROTAC-induced EZH2 degradation and immunity enhancement","authors":"Zhihao Chen ,&nbsp;Yi Tai ,&nbsp;Chuangzhong Deng ,&nbsp;Yameng Sun ,&nbsp;Hongmin Chen ,&nbsp;Tianqi Luo ,&nbsp;Jiaming Lin ,&nbsp;Weiqing Chen ,&nbsp;Huaiyuan Xu ,&nbsp;Guohui Song ,&nbsp;Qinglian Tang ,&nbsp;Jinchang Lu ,&nbsp;Xiaojun Zhu ,&nbsp;Shijun Wen ,&nbsp;Jin Wang","doi":"10.1016/j.biomaterials.2025.123344","DOIUrl":"10.1016/j.biomaterials.2025.123344","url":null,"abstract":"<div><div>Sarcomas are highly malignant tumors characterized by their heterogeneity and resistance to conventional therapies, which significantly limit treatment options. EZH2 is highly expressed in sarcomas, but targeting it is difficult. In this study, we uncovered the non-canonical transcriptional mechanisms of EZH2 in sarcoma and highlighted the essential role of EZH2 in regulating YAP1 through non-canonical transcriptional pathways in the progression of sarcoma. Building on this, we developed YM@VBM, a novel and versatile nano-PROTAC (proteolysis-targeting chimera), by integrating a polyphenol-vanadium oxide system with the EZH2 degrader YM281 PROTAC, encapsulated in methoxy polyethylene glycol-NH₂ to enhance biocompatibility. To further facilitate targeted drug delivery to tumors, YM@VBM nano-PROTACs were incorporated into microneedle patches. Our engineered YM@VBM exhibited multiple functionalities, including the peroxidase-like activity to generate reactive oxygen species, depletion of glutathione, and photothermal effects, specifically targeting sarcoma characteristics. YM@VBM significantly enhanced targeting efficacy via inducing potent EZH2 degradation. Most importantly, it can also activate anti-tumor immunity via excluding myeloid-derived suppressor cells, maturing dendritic cells, and forming tertiary lymphoid structures. Hence, we reveal that YM@VBM presents a promising treatment strategy for sarcoma, offering a multifaceted approach to combat this challenging malignancy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123344"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metal-semimetal Zn–Ge alloy with modified biodegradation behavior and enhanced osteogenic activity mediated by eutectic Ge phases-induced microgalvanic cells","authors":"Kai Chen ,&nbsp;Shan Gao ,&nbsp;Xuenan Gu ,&nbsp;Li Zhao ,&nbsp;Yunan Lu ,&nbsp;Jinwu Bai ,&nbsp;Linjun Huang ,&nbsp;Hongtao Yang ,&nbsp;Yu Qin ,&nbsp;Fang Zhou ,&nbsp;Yongcan Huang ,&nbsp;Yang Lv ,&nbsp;Yufeng Zheng","doi":"10.1016/j.biomaterials.2025.123343","DOIUrl":"10.1016/j.biomaterials.2025.123343","url":null,"abstract":"<div><div>Implants with strong osteogenic properties are crucial for effective bone repair in clinical settings. Recently, biodegradable zinc (Zn)-based metals have shown significant potential as orthopedic implants. However, pure Zn is prone to pitting corrosion and exhibits insufficient osteogenic activity in vivo. To enhance the degradation behavior and osteogenic potential of Zn-based implants, this study developed metal-semimetal Zn–Ge alloys with varying Ge content. The addition of Ge significantly promotes the formation of eutectic Ge phases, refines the microstructure, and improves the mechanical properties of the implants. Incorporating ∼3 wt% Ge into the matrix also facilitates enhanced Zn²⁺ release and ensures uniform biodegradation. Besides, the formation of uniformly distributed heteroid Zn–Ge microgalvanic cells provides a balance between osteogenic and bacteriostatic effects. In vivo tests using a femoral condyle defect model demonstrate that Zn–3Ge implants have favorable osteogenic property and excellent biosafety; the enhanced osteogenic activity of the alloy is attributed to intracellular Zn²⁺ activation of the Wnt signaling pathway, which promotes osteoblast differentiation, cell proliferation, survival, as well as extracellular matrix mineralization and osteogenesis. The incorporation of eutectic Ge phases and effective creation of microgalvanic cells offer a promising strategy for optimizing the biological function of Zn-based implants.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123343"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Living therapeutics: Precision diagnosis and therapy with engineered bacteria","authors":"Ruyan Xie ,&nbsp;Duoyang Fan ,&nbsp;Xiang Cheng ,&nbsp;Ying Yin ,&nbsp;Haohan Li ,&nbsp;Seraphine V. Wegner ,&nbsp;Fei Chen ,&nbsp;Wenbin Zeng","doi":"10.1016/j.biomaterials.2025.123342","DOIUrl":"10.1016/j.biomaterials.2025.123342","url":null,"abstract":"<div><div>Bacteria-based therapy has emerged as a promising strategy for cancer treatment, offering the potential for targeted tumor delivery, immune activation, and modulation of the tumor microenvironment. However, the unpredictable behavior, safety concerns, and limited efficacy of wild-type bacteria pose significant challenges to their clinical translation. Recent advancements in synthetic biology and chemical engineering have enabled the development of precisely engineered bacterial platforms with enhanced controllability, targeted delivery, and reduced toxicity. This review summarize the current progress of engineered bacteria in cancer therapy. We first introduce the theoretical underpinnings and key advantages of bacterial therapies in cancer. Subsequently, we delve into the applications of genetic engineering and chemical modification techniques to enhance their therapeutic potential. Finally, we address critical challenges and future prospects, with a focus on improving safety and efficacy. This review aims to stimulate further research and provide valuable insights into the development of engineered bacterial therapies for precision oncology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123342"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy","authors":"Limin Zhai ,&nbsp;Yifei Gao ,&nbsp;Hao Yang ,&nbsp;Haoyuan Wang ,&nbsp;Beining Liao ,&nbsp;Yuxue Cheng ,&nbsp;Chao Liu ,&nbsp;Jingfeng Che ,&nbsp;Kunwen Xia ,&nbsp;Lingkun Zhang ,&nbsp;Yanqing Guan","doi":"10.1016/j.biomaterials.2025.123345","DOIUrl":"10.1016/j.biomaterials.2025.123345","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by the pathological aggregation of α-synuclein (α-syn) and neuroinflammation. Current gene therapies face challenges in nuclear delivery and resolving pre-existing α-syn aggregates. Here, we developed glucose-and trehalose-functionalized carbonized polymer dots (GT-PCDs) loaded with plasmid DNA (pDNA) for targeted gene delivery and autophagy restoration. The GT-PCDs@pDNA nanoparticles exhibit reactive oxygen species (ROS)-responsive behavior, enabling efficient nuclear entry under oxidative stress conditions. Both in vitro and in vivo studies demonstrated that GT-PCDs@pDNA effectively silenced <em>SNCA</em> gene expression, reduced α-syn aggregates, and restored autophagic flux by promoting transcription factor EB (TFEB) nuclear translocation. Moreover, GT-PCDs@pDNA enhanced blood-brain barrier (BBB) permeability via glucose transporter 1 (Glut-1)-mediated transcytosis, significantly improving motor deficits and reducing neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. This multifunctional nanocarrier system offers a promising strategy for combined gene therapy and autophagy modulation in neurodegenerative diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123345"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin nanocomplex of BCL-2/xL inhibitor reduced platelet toxicity and improved anticancer efficacy in myeloproliferative neoplasm and lymphoma","authors":"Hongxiang Hu ,&nbsp;Chengyi Li ,&nbsp;Yudong Song ,&nbsp;Jizhao Xie ,&nbsp;Qiuxia Li ,&nbsp;Fang Ke ,&nbsp;Bo Wen ,&nbsp;Shaomeng Wang ,&nbsp;Wei Gao ,&nbsp;Duxin Sun","doi":"10.1016/j.biomaterials.2025.123347","DOIUrl":"10.1016/j.biomaterials.2025.123347","url":null,"abstract":"<div><div>The clinical application of BCL-2/xL inhibitors for cancer treatment is limited by the on-target thrombocytopenia. Although APG-1252 was designed to mitigate this issue, platelet toxicity at higher doses in clinical trials restricts dose escalation for greater efficacy. We have developed albumin nanocomplexes of APG-1252 (Nano-1252) to reduce platelet toxicity while improving drug efficacy through enhancing drug delivery to lymphoid organs. Nano-1252 forms stable nanoparticles due to the strong binding affinity between APG-1252 and albumin, reducing the platelet toxicity threshold by fourfold by limiting premature drug release and conversion to its active forms in circulation. Furthermore, Nano-1252 exhibited preferential accumulation in lymphoid organs, leading to enhanced anticancer efficacy in Mantle Cell Lymphoma (MCL) and Myeloproliferative Neoplasms (MPNs) mouse models. Our study not only develops a potential formulation to overcome the current translational barrier of APG-1252 but also reveals novel properties of the well-established albumin nanoformulation, thereby expanding its clinical applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123347"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair","authors":"Ya-Xing Li ,&nbsp;Long-Mei Zhao ,&nbsp;Xiu-Zhen Zhang ,&nbsp;Xi-Kun Ma ,&nbsp;Jing-Qi Liang ,&nbsp;Ting-Jiang Gan ,&nbsp;Heng Gong ,&nbsp;Yan-Lin Jiang ,&nbsp;Ye Wu ,&nbsp;Yu-Ting Song ,&nbsp;Yi Zhang ,&nbsp;Yue Li ,&nbsp;Xiao-Ting Chen ,&nbsp;Cong-Hui Xu ,&nbsp;Xiang-Yu Ouyang ,&nbsp;Jesse Li-Ling ,&nbsp;Hui Zhang ,&nbsp;Hui-Qi Xie","doi":"10.1016/j.biomaterials.2025.123346","DOIUrl":"10.1016/j.biomaterials.2025.123346","url":null,"abstract":"<div><div>Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. <em>In vitro</em>, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123346"},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered metastatic cancer nanovaccine with a TLR7/8 agonist for needle-free intranasal immunization","authors":"Jae Min Jung ,&nbsp;Min Sang Lee ,&nbsp;Young Kyu Seo ,&nbsp;Jung Eun Lee ,&nbsp;Su Yeon Lim ,&nbsp;Dahwun Kim ,&nbsp;Siyan Lyu ,&nbsp;Chaeeun Park ,&nbsp;Byung Deok Kim ,&nbsp;Ju Hwa Shin ,&nbsp;Ji Hyun Lee ,&nbsp;Pin Liu ,&nbsp;Junku Jung ,&nbsp;João Conde ,&nbsp;Thavasyappan Thambi ,&nbsp;Ji Hoon Jeong ,&nbsp;Doo Sung Lee","doi":"10.1016/j.biomaterials.2025.123331","DOIUrl":"10.1016/j.biomaterials.2025.123331","url":null,"abstract":"<div><div>Recent outbreaks and the global spread of infectious diseases increased the need for the development of mucosal vaccines because of their ability to induce both an antigen-specific humoral and cellular immune response. Vaccines are commonly administered via a systemic route which is ineffective at inducing mucosal immunity. Therefore, developing mucosal vaccines is necessary to prevent and treat diseases that could not only elicit mucosal immune responses but also facilitate mass vaccination via a needle-free approach. Despite the benefits of mucosal vaccines, inducing mucosal immunity remains difficult due to the low antigen stability at mucosal sites. Herein, we developed a co-delivery platform using a polymeric nanoparticle carrier to upregulate the immune responses by improving the antigen's stability. Through hydrophobic and ionic interactions, the cationic polymeric nanoparticle composed of secondary bile acid conjugated polyethyleneimine (DA3) can load both TLR7/8 agonist resiquimod (R848) and anionic ovalbumin (OVA) antigen. The DA3/R848/OVA nanovaccine based co-delivery system can boost immune responses through binding affinity with dendritic cells (DCs). The results showed that DA3/R848/OVA could activate DCs better than OVA or OVA + R848. Furthermore, the nanovaccine demonstrated a strong therapeutic effect by significantly suppressing tumor growth in a B16-OVA melanoma model. Additionally, prophylactic immunization with the nanovaccine effectively induced immunological memory, leading to sustained tumor suppression upon challenge. Intranasal delivery of DA3/R848/OVA upregulates the antitumor effect in the metastatic lung tumor foci and the survival rates. These results suggest that intranasal immunization using the DA3/R848/OVA nanovaccine can promote needle-free vaccination.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123331"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848720","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}