BiomaterialsPub Date : 2025-05-08DOI: 10.1016/j.biomaterials.2025.123401
Decui Cheng , Tingting Pan , Xiaoli Wang , Rui Tian , Huizhen Fan , Li Wei , Shiyuan He , Ruonan Dong , Xiangqun Yan , Mei X. Wu , Ruoming Tan , Hongping Qu , Min Lu
{"title":"An advanced inhalable dry powder, mucus-penetrating aerosol platform: Bridging Andrographolide delivery with clinical translation","authors":"Decui Cheng , Tingting Pan , Xiaoli Wang , Rui Tian , Huizhen Fan , Li Wei , Shiyuan He , Ruonan Dong , Xiangqun Yan , Mei X. Wu , Ruoming Tan , Hongping Qu , Min Lu","doi":"10.1016/j.biomaterials.2025.123401","DOIUrl":"10.1016/j.biomaterials.2025.123401","url":null,"abstract":"<div><div>Effective aerosol drug delivery remains a challenge for treating pulmonary diseases due to physiological barriers such as mucus accumulation, biofilm formation, and rapid macrophage clearance. Here, we developed an inhalable honeycomb-like microsphere (HCLplga-Ab) aerosol platform using FDA-approved poly(lactic-co-glycolic acid) (PLGA) and a pore-forming agent. The platform encapsulates Andrographolide, a bioactive compound derived from traditional Chinese medicine, together with a chitosan-ambroxol coating to achieve mucus penetration, sequential drug release, and prolonged retention in the lungs. The large geometric diameter (∼10–15 μm) combined with an optimal aerodynamic size (∼2.57 μm) ensures deep lung deposition while evading alveolar macrophage clearance. In murine models of acute lung injury (ALI), bacterial pneumonia (<em>Klebsiella pneumoniae</em>), and fungal pneumonia (<em>Candida albicans</em>), HCLplga-Ab demonstrated enhanced mucus penetration and biofilm destruction, uniform and prolonged drug retention in the lungs, and significant reduction in inflammation and pathogen burden. This versatile platform bridges traditional medicine with modern aerosol technology, offering a promising solution for respiratory disorders and clinical translation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123401"},"PeriodicalIF":12.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928008","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}
BiomaterialsPub Date : 2025-05-08DOI: 10.1016/j.biomaterials.2025.123403
Bin Du, Qingqing Zou, Xin Wang, Hongqiang Wang, Xiaohai Yang, Qing Wang, Kemin Wang
{"title":"Multi-targeted engineered hybrid exosomes as Aβ nanoscavengers and inflammatory modulators for multi-pathway intervention in Alzheimer's disease","authors":"Bin Du, Qingqing Zou, Xin Wang, Hongqiang Wang, Xiaohai Yang, Qing Wang, Kemin Wang","doi":"10.1016/j.biomaterials.2025.123403","DOIUrl":"10.1016/j.biomaterials.2025.123403","url":null,"abstract":"<div><div>The pathogenesis of Alzheimer's disease (AD) was complex, including excessive deposition of β-amyloid (Aβ), microglia dysfunction, and neuroinflammation. Therefore, single-pathway treatment was not sufficient to ameliorate the multifaceted pathological changes associated with AD. Moreover, the low permeability of blood-brain barrier (BBB) and the lack of AD locus selectivity further limited the intervention efficacy of current AD drugs. In this study, a novel nanoparticle coating was designed by hybridizing the membrane from brain microvascular endothelial cell exosomes and macrophage exosomes, and combining polydopamine nanoparticles, resveratrol and Aβ-targeting aptamers to construct engineered exosomes (RPDA@Rb-A) with multiple targeting capabilities to intervene in Aβ clearance and regulate microglial dysfunction. Based on the homing effect of brain microvascular endothelial cell exosomes and the natural inflammation targeting ability of macrophage exosomes, RPDA@Rb-A can easily penetrate the blood brain barrier and accumulate in the brain inflammation site after capturing Aβ aggregates. RPDA@Rb-A can effectively intervene in AD through multi-pathway, including degraded toxic Aβ aggregates through local heating induced by near-infrared laser irradiation and alleviated neurotoxicity, promoted microglial clearance of Aβ by capturing Aβ, and modulated microglia-induced neuroinflammation by efficient delivery of small molecule drugs. In AD mouse model, the administration of RPDA@Rb-A resulted in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. The engineered exosomes based on membrane hybridization overcome the shortcomings of traditional drug carriers in poor penetration and insufficient targeting to the central nervous system, and provide a potential platform for multi pathways intervention in AD.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123403"},"PeriodicalIF":12.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928007","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}
BiomaterialsPub Date : 2025-05-08DOI: 10.1016/j.biomaterials.2025.123400
Yibo An , Man Li , Pan He , Yubo Tan , Renyuan Liu , Dazhuang Xu , Lijuan Yang , Xinyu Tan , Xiaofei Wen , Gang Liu , Zhixiang Lu
{"title":"Ir-organometallic compounds-mediated internal and external dual-phototheranostics for collaborative antitumor therapy","authors":"Yibo An , Man Li , Pan He , Yubo Tan , Renyuan Liu , Dazhuang Xu , Lijuan Yang , Xinyu Tan , Xiaofei Wen , Gang Liu , Zhixiang Lu","doi":"10.1016/j.biomaterials.2025.123400","DOIUrl":"10.1016/j.biomaterials.2025.123400","url":null,"abstract":"<div><div>Cerenkov light-based excitation represents an attractive alternative to conventional external light excitation, aiming to break the penetration limitations of <em>in vivo</em> optical imaging and therapy. However, Cerenkov light’s inherent deficiency severely restricts its potential applications in tumor theranostic. Herein, we have seamlessly integrated organometallic compounds with radio-phototheranostics for the first time, achieving significant tumor inhibition and the inaugural instance of a radionuclide(<sup>18</sup>F)-activated NIR photosensitizer with a wavelength exceeding 800 nm through the innovative “internal-external attack” design and “two-in-one” internal energy transfer. In this study, coumarin 6 and IR775 derivatives were connected via iridium atoms to construct dual-function iridium-organometallic compounds (IR-C6Ir), combining internal and external responsive molecules for dual phototherapy and Cerenkov light red-shift fluorescence imaging. IR-C6Ir can be preferably accumulated at mitochondrial at the tumor site, inducing excellent anti-tumor effect with a 92.5 % tumor volume reduction at the lower concentration (0.65 μM) and excitation level (800 μCi of <sup>18</sup>F and 0.5 W/cm<sup>2</sup> of 808 nm laser irradiation). In addition, IR-C6Ir-mediated internal and external phototherapy exhibited the synergistic enhancement effect of “1 + 1>2” and achieved tumor multiplex visualization. The combination of internal phototherapy and external phototherapy motifs in one molecule, provides IR-C6Ir with a novel strategy for high-efficiency and low-toxicity phototherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123400"},"PeriodicalIF":12.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935006","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}
BiomaterialsPub Date : 2025-05-07DOI: 10.1016/j.biomaterials.2025.123383
Yuqi Cheng , Lingjin Zhao , Yijing Wen , Zhen Ren , Jiayu Zeng , Rui Shi , Xinqi Cai , Qian Dong , Long Chen , Changwei Lin , Zhuo Chen
{"title":"In vivo spatiotemporal acquisition of metabolic vibrational signatures for unraveling gastric ulcer genesis","authors":"Yuqi Cheng , Lingjin Zhao , Yijing Wen , Zhen Ren , Jiayu Zeng , Rui Shi , Xinqi Cai , Qian Dong , Long Chen , Changwei Lin , Zhuo Chen","doi":"10.1016/j.biomaterials.2025.123383","DOIUrl":"10.1016/j.biomaterials.2025.123383","url":null,"abstract":"<div><div>Metabolic abnormalities in gastric juice usually directly reflect pathological changes of the gastric mucosa. Accurate <em>in-situ</em> gastric metabolic dynamics acquisition is crucial for understanding the occurrence and development of gastric diseases but is challenging. Here, an integrated magnetoplasmonic system (MPS) for long-term spatiotemporal metabolic information profiling and ulcer assessment <em>in vivo</em> is presented. Porous calcium alginate-silver plasmonic hydrogel shell and FeCo@Graphene magnetic core were fabricated into the durable magnetoplasmonic system <em>via</em> a coaxial electrospinning technique. MPS pumped gastric juice through enriching, filtering and magnetic actuation, which had synergistic effect on improving efficient capture of free-metabolites with promotion of 9.76 times. Multiplexed metabolites vibration fingerprint profiles were concurrently determined both in harsh simulated gastric fluid (SGF) and isolated stomach models. We also successfully achieved acquisition of <em>in-situ</em> metabolites changes within rat stomach. Marginal histograms, derived from time-resolved surface-enhanced Raman spectroscopy (SERS) investigations of free small molecules adenine, tyrosine, and phenylalanine, suggested a positive correlation in metabolite levels across different stages. Moreover, ulcers revelation was accomplished with high precision through leveraging spectral dimensionality reduction and random forest classification of SERS profiles. Metabolites correlation analysis indicated that Raman signal appearing at 1602 cm<sup>−1</sup> and 2112 cm<sup>−1</sup> corresponding to phenylalanine and amine exhibited strong positive correlations following ulcer onset. This research represents the first endeavor to profile <em>in-situ</em> metabolic information within stomach and explore their correlations during the genesis of disease, demonstrating its potential in facilitating clinical diagnosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123383"},"PeriodicalIF":12.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935008","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}
BiomaterialsPub Date : 2025-05-07DOI: 10.1016/j.biomaterials.2025.123387
Zheng Li , Guodong Ren , Xuewei Wang , Xiaowan Li , Lingwen Ding , Jianwei Zhu , Yajie Zhang , Chengwu Zhang , Jianhua Zou , Xiaoyuan Chen
{"title":"Tumor microenvironment responsive nano-PROTAC for BRD4 degradation enhanced cancer photo-immunotherapy","authors":"Zheng Li , Guodong Ren , Xuewei Wang , Xiaowan Li , Lingwen Ding , Jianwei Zhu , Yajie Zhang , Chengwu Zhang , Jianhua Zou , Xiaoyuan Chen","doi":"10.1016/j.biomaterials.2025.123387","DOIUrl":"10.1016/j.biomaterials.2025.123387","url":null,"abstract":"<div><div>Proteolysis Targeting Chimeras (PROTAC) technology has garnered great attention due to its advantages in targeted protein degradation, promising its potential for treating malignant cancer. Nevertheless, the inherent drawbacks of PROTAC technology hinder its clinical translation. The integration of nanotechnology with PROTAC molecules to create nano-PROTACs for combined therapy offers a promising solution. Among the various cancer treatment methods, phototherapy is considered the optimal choice to integrate with specific PROTACs due to its proven effectiveness and non-invasive nature. Herein, a nano-PROTAC formulation (ARV@PEG-ICG) consisting of a phototherapeutic agent named indocyanine green functionalized polyethylene glycol (PEG-ICG) and a BRD4 degrader (ARV-825) was fabricated for cancer photo-immunotherapy. Activated by acidic tumor microenvironment (TME), ARV@PEG-ICG nanoparticles (NPs) will decompose rapidly for ARV delivery. PEG-ICG generated abundant ROS with laser irradiation, downregulating the expression of Bcl-xL and inducing the cleavage of PARP to stimulate cell apoptosis. Furthermore, the degradation of BRD4, a transcriptional cofactor, inhibited nitric oxide synthase (iNOS) generation to improve phototherapeutic efficacy. In a 4T1 breast tumor model, dying 4T1 cells released tumor associated antigens (TAAs) to serve as the immunogenic cell death (ICD) inducer, facilitating DC maturation and T cell activation and amplifying systemic immune response. The distant tumor growth can also be inhibited due to the activation of long-term immune response. Overall, the current study aims to combine typical PROTAC with functional nanomaterials to form nano-PROTAC with high performance for PROTAC delivery mediated cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123387"},"PeriodicalIF":12.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924392","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}
BiomaterialsPub Date : 2025-05-07DOI: 10.1016/j.biomaterials.2025.123376
Zhuocheng Lyu , Yuezhou Wu , Fei Hu , Xu Zheng , Dajun Ma , Zhenjiang Xu , Yurun Ding , Xuesong Liu , Shicheng Huo
{"title":"Controlled release of ionic carrier hydrogels for sequential immunomodulation to facilitate stage-specific treatment of infectious wound","authors":"Zhuocheng Lyu , Yuezhou Wu , Fei Hu , Xu Zheng , Dajun Ma , Zhenjiang Xu , Yurun Ding , Xuesong Liu , Shicheng Huo","doi":"10.1016/j.biomaterials.2025.123376","DOIUrl":"10.1016/j.biomaterials.2025.123376","url":null,"abstract":"<div><div>Infected wounds present a significant clinical challenge, exacerbated by antibiotic resistance, which complicates effective treatment. This study introduces a hydrogel (CC/AP@CM) embedded with core-shell bioactive glass nanoparticles designed for the controlled, sequential release of copper (Cu<sup>2+</sup>) and magnesium (Mg<sup>2+</sup>) ions. The hydrogel is crosslinked via a Schiff base reaction, endowing it with injectable, self-healing, and adhesive properties. Notably, the bilayer structure of the bioactive glass within the hydrogel allows an initial release of Cu<sup>2+</sup> ions to trigger an early-stage pro-inflammatory and antimicrobial response, followed by Mg<sup>2+</sup> ions that support tissue repair and an anti-inflammatory environment. This design aligns with natural wound healing stages, promoting a shift in macrophage polarization from the M1 to M2 phenotype, effectively balancing antibacterial defense with tissue regeneration. The hydrogel demonstrated robust antibacterial efficacy against MRSA, increased angiogenesis, and enhanced fibroblast proliferation and migration in vitro. In a murine wound model, it significantly accelerated wound closure and immune activation, including responses from dendritic cells and T cells. These findings suggest that this hydrogel, through its stage-specific immunomodulatory properties and temporally controlled ion release, offers a promising strategy for treating complex wound infections, supporting both immune defense and tissue healing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123376"},"PeriodicalIF":12.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928009","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}
BiomaterialsPub Date : 2025-05-07DOI: 10.1016/j.biomaterials.2025.123398
Zhifang Wang , Fanrou Zhang , Bingshuai Zhou , Liheng Sun , Bailong Liu , Min Liu , Shimeng Wang , Lin Xu , Haipeng Liu , Biao Dong
{"title":"Gradient-driven deep penetration of self-electrophoretic nanoparticles in acidic tumor microenvironments for enhanced antitumor therapy","authors":"Zhifang Wang , Fanrou Zhang , Bingshuai Zhou , Liheng Sun , Bailong Liu , Min Liu , Shimeng Wang , Lin Xu , Haipeng Liu , Biao Dong","doi":"10.1016/j.biomaterials.2025.123398","DOIUrl":"10.1016/j.biomaterials.2025.123398","url":null,"abstract":"<div><div>Difficulty of nanomedicines to effectively penetrate the tumor core and achieve effective killing of tumor stem cells is an important factor leading to recurrence, metastasis and drug resistance of tumors. Strategies based on the tumor microenvironment offer new perspectives and approaches to address the challenges associated with deep tumor treatment. Here, we designed novel MgF<sub>2</sub>@L-Arg nanoparticles (ML NPs) by integrating basic L-arginine into MgF<sub>2</sub>. Under the endogenous acid gradient within the tumor, ML NPs selectively protonate their proximal amines, leading to spatial charge asymmetry. This promotes the sustained diffusion and permeation of ML NPs deep into the tumor, achieving a penetration distance of up to 197 μm. Moreover, aside from enabling synergistic effects in sonodynamic therapy (SDT) and gas therapy, ML NPs can reduce the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and heat shock protein 70 (HSP 70) within tumor cells, induce immunogenic cell death, and bind to the co-stimulatory molecule LFA-1 on the surface of tumor cells, thereby enhancing the specific cytotoxicity of CD8<sup>+</sup> T cells. This mechanism significantly improves the immune response against cancer cells and effectively suppresses tumor metastasis. Our research proposes a viable new strategy for the deep penetration of nanoparticles into tumors and for effective deep tumor treatment, demonstrating the tremendous potential of such materials in enhancing anti-tumor efficacy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123398"},"PeriodicalIF":12.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924391","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":"Photoactivated in-situ engineered-bacteria as an efficient H2S generator to enhance photodynamic immunotherapy via remodeling the tumor microenvironment","authors":"Jiajia Yin, Wenyu Sun, Hongjie Xiong, Wenyan Yao, Xiaohui Liu, Hui Jiang, Xuemei Wang","doi":"10.1016/j.biomaterials.2025.123388","DOIUrl":"10.1016/j.biomaterials.2025.123388","url":null,"abstract":"<div><div>Based on the unique biological advantages of bacteria and their derivatives, biosynthetic nanomaterials have been widely used in the field of tumor therapy. Although conventional bacterial treatments demonstrate potential in activating tumor immunity, their efficacy in inhibiting tumor growth remains constrained. In this study, a photoactivated hydrogen sulfide (H<sub>2</sub>S) generator was successfully prepared by in-situ engineering of bacteria, after Pt/MoS<sub>2</sub> nanocomposites were in-situ generated by <em>Escherichia coli</em> (<em>E. coli</em>) and loaded with photosensitizer Ce6. This engineered-bacteria has been proved to have good tumor targeting ability and can enhance the effect of photodynamic therapy in the hypoxic tumor microenvironment. While reactive oxygen species (ROS) is effectively released, the fragmentation of bacteria can accelerate the release of abundant H<sub>2</sub>S, and promote tumor-specific H<sub>2</sub>S gas therapy, which can effectively remodel the tumor microenvironment and promote the activation of anti-tumor immunotherapy. This engineered bacteria not only improves the tumor specificity and effectiveness of H<sub>2</sub>S treatment, but also provides a new idea for nanomaterials in bacterial-mediated synergistic cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123388"},"PeriodicalIF":12.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916421","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}
BiomaterialsPub Date : 2025-05-06DOI: 10.1016/j.biomaterials.2025.123392
Xinshuang Zhang , Dong Luo , Jie Hu , Kangxiu Wu , Shuyi Jia , Xueyi Li , Songyin Huang , Houbing Zhang , Dokyun Kim , Yuzhi Hong , Liping Zhao , Menghua Xiong , Yan Bao
{"title":"Selective recognition of bacterial phospholipids by antimicrobial peptides: Employing a host-guest-mediated competitive inhibition strategy","authors":"Xinshuang Zhang , Dong Luo , Jie Hu , Kangxiu Wu , Shuyi Jia , Xueyi Li , Songyin Huang , Houbing Zhang , Dokyun Kim , Yuzhi Hong , Liping Zhao , Menghua Xiong , Yan Bao","doi":"10.1016/j.biomaterials.2025.123392","DOIUrl":"10.1016/j.biomaterials.2025.123392","url":null,"abstract":"<div><div>The distinct phospholipid compositions of bacterial and mammalian cell membranes offer a promising target for the development of antimicrobial peptides (AMPs). However, distinguishing between the similarly charged anionic phospholipids—bacterial phosphatidylglycerol (PG) and mammalian phosphatidylserine (PS)—poses a significant challenge. Here we introduce a competitive inhibition strategy that leverages host-guest interactions to enable AMPs to selectively recognize PG without engaging with PS. After analyzing the binding interactions of various radially amphiphilic AMPs (RAPs), host molecules, and phospholipids, we discovered that a RAP, named C6HO, exhibited a higher affinity for cucurbit[7]uril (CB[7]) compared to PS, yet a lower affinity than for PG. Consequently, CB[7] functions as a competitive inhibitor: by forming a complex with C6HO upon simple mixing, it prevents C6HO from interacting with PS. Notably, PG can outcompete CB[7] for binding to C6HO within the complex, leading to the aggregation of PG molecules and the subsequent disruption of membranes rich in PG. Furthermore, the competitive inhibitor CB[7] effectively neutralizes C6HO's cytotoxic effects on mammalian cells while preserving the antimicrobial potency of C6HO. In vivo experiments in a subcutaneous infection model demonstrated that CB[7] reduced both systemic and local toxicity of C6HO without compromising its antimicrobial efficacy. Our study presents a strategy for the specific recognition of bacterial phospholipids and the design of highly selective AMPs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123392"},"PeriodicalIF":12.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935007","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}