Colloids and Surfaces B: Biointerfaces最新文献

{"title":"Esterase-activatable dimeric HDAC inhibitor nanotherapeutics for enhanced lymphoma epigenetic therapy","authors":"Tongyu Li ,&nbsp;Wanchuan Zhuang ,&nbsp;Shufang Fan ,&nbsp;Ping Yi ,&nbsp;Guifang Ouyang ,&nbsp;Wenbin Qian","doi":"10.1016/j.colsurfb.2026.115416","DOIUrl":"10.1016/j.colsurfb.2026.115416","url":null,"abstract":"<div><h3>Background</h3><div>Despite advances in lymphoma therapy, significant challenges persist including R-CHOP resistance and CAR-T toxicity. Hydroxamate-based histone deacetylase inhibitors (HDACi) like vorinostat (SAHA) offer epigenetic therapeutic potential but are limited by poor bioavailability and rapid clearance.</div></div><div><h3>Methods</h3><div>To overcome these barriers, we rationally designed an esterase- activatable dimeric prodrug by conjugating two SAHA molecules <em>via</em> a glutaric acid linker (SAHA-cc-SAHA). This prodrug co-assembled with DSPE-PEG₂₀₀₀ into nanoparticles (cc-diSAHA NPs). The system was characterized (DLS/TEM), and its drug release profile was assessed with/without porcine liver esterase (PLE). Antitumor activity was evaluated in EL4/A20 lymphoma cells (apoptosis/cycle assays, etc) and EL4 allograft. Transcriptomic mechanisms were deciphered by RNA-seq.</div></div><div><h3>Results</h3><div>The cc-diSAHA NPs were uniform spheres (∼74 nm, PDI = 0.187) with excellent colloidal stability and minimal drug leakage (&lt;4 % in 7 days), while enabling rapid drug release upon esterase stimulation (92.4 % within 7 h with PLE). <em>In vitro</em>, they demonstrated broad-spectrum anti-lymphoma activity, inducing G₀/G₁ arrest and apoptosis, albeit with delayed kinetics versus free formulations, consistent with a sustained-release profile. Transcriptomics revealed multifaceted mechanisms, including potent activation of interferon-mediated immunogenic stress and hematopoietic differentiation, alongside enriched adhesion and redox metabolism pathways. <em>In vivo</em>, intravenous cc-diSAHA NPs suppressed EL4 tumor growth significantly more than oral SAHA (819.36 vs 1594.40 mm³; <em>p</em> &lt; 0.01), without inducing systemic toxicity or organ damage.</div></div><div><h3>Conclusion</h3><div>This nanoplatform overcomes HDACi delivery barriers by reconciling the stability-activation paradox, providing a therapeutically viable option for lymphoma patients ineligible for standard intensive therapies.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115416"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975463","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":"Visualizing intracellular and extracellular cell-mineral interactions in a three-dimensional breast tumor model","authors":"Amit Cohen ,&nbsp;Einat Nativ-Roth ,&nbsp;Netta Vidavsky","doi":"10.1016/j.colsurfb.2026.115450","DOIUrl":"10.1016/j.colsurfb.2026.115450","url":null,"abstract":"<div><div>Microcalcifications (MCs) in breast tissue, with particularly high prevalence in precancerous lesions, such as ductal carcinoma <em>in situ</em> (DCIS), represent important diagnostic markers for cancer screening. Two primary crystal types, hydroxyapatite (HA) and calcium oxalate dihydrate (COD), occur within breast tumor microenvironments. Evidence from clinical samples has demonstrated that COD is usually found as individual crystals, whereas HA tends to aggregate. Notably, MC crystal types and properties are linked to malignancy, with COD crystals being associated with benign lesions. <em>In-vitro</em> studies have shown that COD crystals can suppress cancerous behavior, whereas HA often promotes it. However, crystal–cell interactions in tumor microenvironments that may explain differential responses to COD and HA remain poorly investigated. Thus, to examine mineral–cell interactions based on cell malignancy potential and crystal type, a three-dimensional multicellular model consisting of precancerous and cancerous human cell lines was employed. Through cryo-scanning electron microscopy (cryo-SEM), we visualized mineral–biological interfaces and showed that cellular types and processes govern crystal aggregation patterns and distribution. Both precancerous and invasive models exhibited enhanced COD crystal packing, while HA crystals formed predominantly loose structures with notable malignancy-dependent variations. In all cases, crystals were found both extra- and intracellularly, the latter being located inside vesicles in some cases, especially for COD crystals. The predominance of intracellular vesicles containing COD crystals rather than HA crystals across both cell types may reflect enhanced cellular processes that promote reduced malignant behavior. These findings may explain why seemingly similar calcium-containing minerals associate differently with malignancy and induce distinct cellular responses.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115450"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008179","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":"Phenylboronic acid modification and small-molecule assembly to enhance the safety of resiquimod and its synergistic anti-tumor efficacy with paclitaxel","authors":"Ziqi Liu ,&nbsp;Manzhen Li ,&nbsp;Pengxin Li ,&nbsp;Miao Chen ,&nbsp;Tianchi Cui ,&nbsp;Yaoyao Guo ,&nbsp;Xiangtao Wang","doi":"10.1016/j.colsurfb.2026.115449","DOIUrl":"10.1016/j.colsurfb.2026.115449","url":null,"abstract":"<div><div>To overcome the systemic toxicity and poor tumor targeting of the TLR7/8 agonist R848, this study developed a derivative by attaching a phenylboronic acid (PBA) group to R848. The resultant R848-PBA retain the immune activation of R848, easily assembly with indocyanine green (ICG) into nanoparticles (R-P@ICG NPs), which demonstrated greatly improved safety and excellent tumor targetability. Inspired by this, paclitaxel (PTX) was also conjugated with PBA and self-assembly with chlorogenic acid (CA) into nanoparticles (P-P@CA NPs). In 4T1 tumor mice mode, P-P@CA NPs induced significant immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) while R-P@ICG NPs synergistically promoted dendritic cells (DCs) maturation and trigger both innate and adaptive immune responses. This combined therapy achieved a tumor inhibition rate of 93.2 % and a tumor eradication rate of 33.3 %, accompanied by a long-lasting anti-tumor immune memory and no evident toxic effect. Phenylboronic acid modification and self-assembly with small molecules presents a promising strategy to realize the clinical translation of the synergistic antitumor efficacy of R848-based chemoimmunotherapy and chemotherapeutics by alleviated systemic toxicity and endowed tumor targetability.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115449"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117082","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":"Organic nano-quantum dots of salvianolic acid B modified with photosensitive cypate for diagnosis and treatment of myocardial","authors":"Na Wang ,&nbsp;Ye Zhang ,&nbsp;Wen Huang ,&nbsp;Wei Du ,&nbsp;Chunhua Ma ,&nbsp;YuQiang Fang ,&nbsp;Chunyu Zeng","doi":"10.1016/j.colsurfb.2026.115414","DOIUrl":"10.1016/j.colsurfb.2026.115414","url":null,"abstract":"<div><div>Salvianolic acid B (SaB) demonstrates significant cardioprotective effects against myocardial ischemia–reperfusion injury (I/R). However, its clinical application is limited by rapid metabolism and poor bioavailability. To address this, we synthesized SaB-loaded organic quantum dots (SaB@qd) via a hydrothermal method and functionalized them with the near-infrared (NIR) dye cypate (SaB@qd@Cy). Proteomic analysis of cardiac tissues from I/R model rats identified SIRT2 as a key downregulated protein. Molecular docking and cell membrane chromatography confirmed SaB as a natural SIRT2 agonist, binding specifically to the SER-263 residue. SaB@qd@Cy enhanced myocardial SaB accumulation by 3.2-fold compared to free SaB (P &lt; 0.01). In vivo, SaB@qd@Cy reduced the infarct area by 41 % (compared to 28 % reduction by mitochondrial-targeted CoQ10 nanoparticles) and attenuated inflammatory cytokine expression (IL-1β, TNF-α) via the SIRT2/NLRP3 pathway. Additionally, cypate enabled real-time NIR imaging of ischemic borders, with a temperature increase of 15.3 ± 1.2°C under 808 nm laser irradiation. This study presents a novel theranostic nanoplatform that integrates natural compounds with photoresponsive quantum dots for targeted therapy and intraoperative imaging in I/R management.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115414"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915404","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":"High efficacy and biocompatibility: Application and biological evaluation of LA67 liposome in colon cancer therapy","authors":"Nuoya Wang ,&nbsp;Jingyuan Wang ,&nbsp;Zhenghu Yuan ,&nbsp;Zhonggao Gao ,&nbsp;Mingji Jin ,&nbsp;Minhu Cui","doi":"10.1016/j.colsurfb.2026.115429","DOIUrl":"10.1016/j.colsurfb.2026.115429","url":null,"abstract":"<div><div>In this study, a single-component liposomal nano-delivery system (LA67@Lipo) was developed for the new antitumor drug LA67. The resulting liposomes were homogenous, spherical vesicles with an average particle size of approximately 109.2 ± 3.8 nm, polydispersity index value of 0.147, and zeta potential of –8.78 ± 0.29 mV, demonstrating excellent dispersibility and stability. The drug encapsulation efficiency surpassed 89.7 ± 3.5 %. Liposomes exhibited a sustained <em>in vitro</em> drug release profile. LA67@Lipo markedly improved internalization by C26 colon cancer cells, effectively inhibiting cell proliferation and inducing apoptosis. In a C26 tumor-bearing mouse model, intravenously administered LA67@Lipo exhibited superior tumor suppression effects. It inhibited Ki-67 and CD31 and decreased intratumoral microvessel density without inducing systemic toxicity, demonstrating excellent <em>in vivo</em> antitumor efficacy and good biosafety. In conclusion, LA67@Lipo is an efficacious therapeutic approach for colon cancer. This optimized design of LA67@Lipo meets clinical demand for \"safety, efficacy, and manufacturability\" while addressing batch-to-batch reproducibility in nanomedicine.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115429"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915408","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":"Synergistic eradication of drug-resistant bacteria by rhamnolipids and pyocyanin via combined membrane permeabilization and oxidative stress","authors":"Li Luo ,&nbsp;Deyu Zhang ,&nbsp;Mengqian Zhao ,&nbsp;Jing Chen ,&nbsp;Jian Yin ,&nbsp;Xuwei Long","doi":"10.1016/j.colsurfb.2026.115418","DOIUrl":"10.1016/j.colsurfb.2026.115418","url":null,"abstract":"<div><div>The threat of antimicrobial resistance (AMR) necessitates novel approaches against multidrug-resistant pathogens. This study pioneers a synergistic antibacterial strategy using rhamnolipids (RLs), a membrane-disrupting biosurfactant, and pyocyanin (Pyo), a redox-active compound, both produced by <em>Pseudomonas aeruginosa</em>. Results demonstrate that RLs compromise bacterial membrane and biofilm integrity, enhancing Pyo penetration. Intracellular Pyo then induces lethal oxidative stress <em>via</em> ROS generation and respiration inhibition. The combination exhibits remarkable synergy (FICI ≤0.375), reducing the required Pyo concentration by 16–64-fold against resistant strains. This dual-agent system not only ensures effective antibacterial activity but also maintains low mammalian cell cytotoxicity. Through complementary, lower-risk mechanisms, the RLs/Pyo pair presents a promising platform for treating intractable infections.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115418"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915409","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":"Beta vulgaris-derived exosome-like nanovesicles mitigate photoaging by attenuating oxidative stress and promoting collagen biosynthesis","authors":"Jian Zhou ,&nbsp;Mengen Guo ,&nbsp;Yanjin Peng ,&nbsp;Wenjie Xu ,&nbsp;Xinyan Hao ,&nbsp;Yucheng Tang ,&nbsp;Tiantian Tang ,&nbsp;Junyong Wu ,&nbsp;Daxiong Xiang","doi":"10.1016/j.colsurfb.2025.115412","DOIUrl":"10.1016/j.colsurfb.2025.115412","url":null,"abstract":"<div><div>Photodamage, primarily induced by ultraviolet (UV) radiation, is a major contributor to skin aging and a significant dermatological challenge. While conventional anti-aging strategies exist, their limited efficacy and potential side effects necessitate the exploration of safer and more effective alternatives. Here, we report on a novel anti-photoaging nanotherapy using exosome-like nanovesicles (BVNVs) derived from edible beet (<em>Beta vulgaris</em>). We demonstrate that BVNVs effectively mitigate UV-induced skin damage through a multi-faceted mechanism. <em>In vitro</em> experiments showed that BVNVs significantly promote the expression of key extracellular matrix (ECM) protein, collagen I (COL-1), while markedly inhibiting the expression of collagen-degrading enzyme, matrix metalloproteinase 1 (MMP1). Mechanistically, BVNVs treatment robustly attenuated UV-induced oxidative stress, as evidenced by a substantial reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and an enhancement in antioxidant enzyme superoxide dismutase (SOD) activity. Furthermore, BVNVs reduced cellular senescence markers, including senescence-associated β-galactosidase (SA-β-Gal), in UV-irradiated skin cells. Consistent with our <em>in vitro</em> findings, <em>in vivo</em> studies on a photodamaged skin model revealed that topical application of BVNVs effectively restored skin structure and function. These findings highlight BVNVs as a promising, biocompatible, and sustainable nanoplatform for anti-photoaging therapy. Our study not only provides a scientific basis for developing new skin care solutions from natural sources but also presents a compelling case for harnessing plant-derived nanovesicles in addressing oxidative stress-related dermatological conditions.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115412"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964572","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":"A self-adapting DNA-crosslinked hydrogel reprograms macrophage polarization and angiogenesis for synergistic repair of diabetic wounds","authors":"Wenxin Feng ,&nbsp;Yi Gao ,&nbsp;Zexin Peng ,&nbsp;Hongxu Liu ,&nbsp;Qiuwen Yang ,&nbsp;Xin Gao ,&nbsp;Yi Jin ,&nbsp;Xinjian Yang ,&nbsp;Enjun Wang","doi":"10.1016/j.colsurfb.2026.115465","DOIUrl":"10.1016/j.colsurfb.2026.115465","url":null,"abstract":"<div><div>Chronic diabetic wounds continue to be a major therapeutic challenge due to sustained inflammation, impaired angiogenesis, and disrupted extracellular matrix remodeling. Partial conventional dressings and growth factor therapies often act passively or release agents independently, lacking coordinated regulation of immune and vascular responses necessary for effective healing. In this study, we report a self-adapting DNA-crosslinked silk fibroin hydrogel designed to reprogram macrophage polarization and angiogenesis for coordinated diabetic wound repair. The hydrogel integrates <span>L</span>-arginine-loaded bone marrow mesenchymal stem cell-derived exosomes within a pH-responsive DNA conformational switch, in which cholesterol-modified DNA strands undergo an acidic pH-induced duplex–to–i-motif transition. This structural change disrupts hydrogen bonding between complementary strands, enabling precise release of therapeutic cargos in the acidic diabetic wound microenvironment. In vitro, the hydrogel effectively induced macrophage M1-to-M2 repolarization, enhanced endothelial cell proliferation, migration, and angiogenesis. In diabetic mouse models, it accelerated reepithelialization, enhanced CD31 and vascular endothelial growth factor expression, suppressed pro-inflammatory cytokines, and restored collagen deposition. This self-adapting, dual-modulatory hydrogel establishes a self-reinforcing “immune-vascular” feedback loop, enabling synchronized immunoregulation and angiogenesis. The findings highlight a programmable therapeutic strategy for reversing chronic inflammatory microenvironments and promoting functional tissue regeneration in diabetic wounds.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115465"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035619","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":"Chitosan-based bimodal photosensitive system: Synergistic realization of visible light viscosity imaging and near-infrared type I photodynamic therapy","authors":"Bo Zhao ,&nbsp;Xinjian Cheng ,&nbsp;Junyu Chen ,&nbsp;Chenghua Zhang ,&nbsp;Jun Liu","doi":"10.1016/j.colsurfb.2026.115432","DOIUrl":"10.1016/j.colsurfb.2026.115432","url":null,"abstract":"<div><div>The integration of bioimaging and photodynamic therapy (PDT) joins real-time visualization with spatially controlled therapeutic activation, thus presenting a promising theranostic platform for precision oncology. However, the clinical translation of conventional photosensitizers suffers from limited tissue penetration and potential photodamage. To overcome these shortcomings, we proposed a NIR responsive system in this work. A naphthalimide-based small molecule (NQL) was synthesized, followed by oligo-chitosan conjugation through Schiff base formation, yielding the water-soluble probe CS-NQL. CS-NQL exhibits a twisted intramolecular charge transfer (TICT) state. It also has the capability to target lysosomes. This enables CS-NQL to respond to environmental viscosity, with target lysosomes. The CS-NQL was then electrostatically self-assembled with DNA to form nanoparticles (CS-NQL@DNA NPs). These nanoparticles (NPs) can generate reactive oxygen species (ROS) under 660 nm laser irradiation, exhibiting photosensitivity. Further detection using commercial reagents revealed this photosensitivity stems via Type I process. Critically, this oxygen-independent mechanism retained the ability to generate ROS under hypoxia, overcoming the limitations of the tumor microenvironment. Under 660 nm laser irradiation (0.4 W/cm²) for 20 min, NPs generate ROS, leading to apoptosis in over 90 % of HeLa cells and demonstrating antitumor effects. In vivo experiments, it is demonstrated that the NPs exhibited PDT after 30 min of 660 nm laser irradiation, achieving significant tumor suppression.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115432"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924118","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":"Amino acid-based modulation of enzyme-metal organic frameworks (MOFs) composites: A conceptual perspective","authors":"Pravin D. Patil ,&nbsp;Niharika Gargate ,&nbsp;Manishkumar S. Tiwari ,&nbsp;Ajay N. Phirke ,&nbsp;Shamraja S. Nadar","doi":"10.1016/j.colsurfb.2026.115437","DOIUrl":"10.1016/j.colsurfb.2026.115437","url":null,"abstract":"<div><div>An amino acid-assisted fabrication of enzyme-MOF composites represents a novel approach for enhancing biocatalyst performance through molecular-level interactions. The flexible roles of amino acids as modulators, linkers, defect inducers, and microenvironmental regulators inside MOF systems for enzyme immobilization are extensively investigated in this review. This review examines explicitly amino acids in four key aspects: (i) modulation of MOF attributes including physico-chemical stability, surface functionalization and microenvironment, morphology, and defect engineering; (ii) enhancement of immobilized enzyme properties such as catalytic activity, stability, kinetic parameters, and reusability; (iii) their role as organic cross-linkers in univariate and multivariate amino acid-based MOFs; and (iv) mechanistic insights into nucleation, self-assembly, and enzyme-MOF interactions. Mechanistic knowledge helps define several roles that natural amino acids play in guiding MOF nucleation, fostering self-assembly, and enhancing catalytic activity. Their capacity to modify surface chemistry, maintain enzyme conformation, and increase active-site exposure is especially underlined to improve the biocatalyst's thermal, chemical, and reusability profiles. Furthermore, amino acid-mediated defect engineering of MOF can enhance pore structure and loading efficiency. Despite scattered experimental demonstrations, this review views amino acids as next-generation molecular tools for tailoring MOF-enzyme systems, providing a template for the rational construction of composites. The work concludes by identifying current limitations and outlining future opportunities in amino acid-guided bio-hybrid catalyst development for industrial biotransformation.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"261 ","pages":"Article 115437"},"PeriodicalIF":5.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975462","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}