Early non-invasive diagnosis of liver fibrosis remains a significant clinical challenge. This study aimed to develop type IV collagen-targeted phase-change nanoparticles (AC-IV-PFP@NPs) for ultrasound molecular imaging (UMI), allowing accurate staging of early-stage liver fibrosis. AC-IV-PFP@NPs were prepared by conjugating anti-collagen IV antibody (AC-IV) to perfluoropentane-encapsulated liposomes carbodiimide coupling. Physicochemical properties were characterized using transmission electron microscopy, dynamic light scattering, and confocal microscopy. In CCl-induced fibrotic rats representing METAVIR stages S0-S4, the targeted nanoparticles were administered intravenously. The nanoparticles displayed spherical morphology with a mean diameter of 307.92 ± 4.16 nm, high AC-IV conjugation efficiency (78.94 ± 2.83%), and a favorable biosafety profile (cell viability >87% at 6 mg mL). Targeting specificity was validated both and , with fluorescence imaging showing a 3.8-fold increase in binding to fibrotic collagen IV relative to non-targeted controls ( < 0.001). CEUS signal intensity peaked at 30 min post-injection and showed a strong positive correlation with the fibrosis stage ( = 0.725, < 0.001). ROC analysis demonstrated high diagnostic accuracy for early fibrosis: an area under the curve (AUC) of 0.949 for distinguishing S0 from S1-S4 (sensitivity 85.5%, specificity 91.7%) and an AUC of 0.923 for separating S0-S1 from S2-S4 (sensitivity 90.7%, specificity 79.2%). To date, AC-IV-PFP@NPs represent the first type IV collagen-targeted UMI platform for liver fibrosis staging in rats, offering non-invasive, real-time assessment with high sensitivity for early-stage disease (S1-S2). This approach addresses the limitations of biopsy and conventional imaging and offers a promising and transformative approach for clinical fibrosis management.

Proton-conducting biopolymers have gained significant attention in various fields, such as energy-related applications, ion exchange membranes, bioelectronics, and biomedical applications. To understand their proton transport mechanisms, it is crucial to distinguish the contributions of water, particularly near the surface functional groups of the dopants (carbon dots, C-Dots) and in the vicinity of the side chain functional groups of proteins in the biopolymer. In this study, we investigate the role of surface functional groups (dopants/biopolymers) in mediating proton conduction across biopolymers (protein-based) by the doping of blue-, green-, and red-emitting C-Dots (with different extents of oxygen-containing groups) into the biopolymer. We measure the proton conduction across the doped biopolymers with varying percentages of water and different extents of oxo-group-enriched dopants with the same internal structure to understand the role of surface functional groups in individual matrices and enhance the conductivity in a controlled way. This approach may provide insights into the proton conduction pathways in biological systems and aid in the development of bioprotonic devices.

: Early diagnosis of prostate cancer is critical for improving prognosis, but current detection techniques face limitations such as low sensitivity, high cost, and radiation risks. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in prostate cancer cells and a promising diagnostic and prognostic indicator. This study aims to develop a PSMA-targeted ultrasound contrast agent based on nanobody-modified gas vesicles (GVs) for early diagnosis of prostate cancer. : GVs were extracted from . PSMA-targeting nanobodies (Nb-PSMA) were synthesized by . PSMA-targeted gas vesicles (PSMA-GVs) were prepared by coupling Nb-PSMA to GVs the intermediate coupling agent Mal-PEG-NHS. Control vesicles were prepared similarly. The targeting specificity of PSMA-GVs towards prostate cancer cells was assessed by flow cytometry and confocal microscopy using PSMA-positive PC-3 cells. contrast-enhanced ultrasound imaging of PSMA-GVs was performed in prostate cancer-bearing mice at early and advanced stages. The biocompatibility of PSMA-GVs was assessed by hemolysis tests, CCK8 cytotoxicity assays, serum biochemical assays and HE staining. : PSMA-GVs exhibited a uniform size, with a hydrodynamic diameter of 267.73 ± 2.86 nm, and showed a high specific binding ability to PC3 cells. ultrasound imaging of prostate cancer-bearing mice showed that PSMA-GVs had significantly slower tumor signal attenuation than Con-GVs. Our and experiments demonstrated that PSMA-GVs could bind to prostate cancer cells with higher specificity, generating stronger and longer-lasting molecular imaging signals in tumors, which presented significant advantages over Con-GVs. Immunofluorescence confirmed that PSMA-GVs crossed the vascular wall, entered the peritumoral vascular space, bound to tumor cells, and enabled PSMA-targeted molecular imaging. Additionally, PSMA-GVs showed good biocompatibility. : Our study provides a new strategy for early ultrasound molecular imaging diagnosis of prostate cancer.

Four-dimensional (4D) printing enables the creation of dynamic structures that can change, altering their shape, properties, or functionality in response to stimuli over time by incorporating time as a fourth dimension. This revolutionary approach has gotten significant attention across various fields, with recent advancements in integrating smart biomaterials, biological components, and living cells into dynamic, three-dimensional (3D) constructs. Among the myriad of biomaterials available, protein-based (PB) polymers have emerged as promising due to their inherent biocompatibility, biodegradability, and ability to interact with and mimic the extracellular matrix (ECM). This review provides a comprehensive overview of 4D bioprinting, involving PB bioinks, and explores key principles, mechanisms, strategies, and types. It discusses essential requirements, such as printability, biodegradation, and mechanical integrity, as well as strategies for designing stimuli-responsive 4D bioinks. Furthermore, it comprehensively explores emerging trends in applying these bioinks for the 4D bioprinting of tissue scaffolds and their utility in disease modeling. Finally, it addresses current challenges and prospects, aiming to provide readers with a thorough understanding of recent developments in this groundbreaking technology towards adaptability in regenerative medicine and disease models.

The use of platelet-derived membranes as functional biomaterials has emerged as a promising solution to overcome major limitations in nanoparticle-based drug delivery and diagnostic platforms. These biologically inspired interfaces offer a unique combination of immune evasion, biocompatibility, and receptor-mediated targeting capabilities. This PRISMA-based systematic review synthesizes research from 2014 to 2024 on the use of platelet membranes to engineer hybrid nanocarriers for targeted delivery and detection. We critically examine strategies for membrane extraction (, ultrasonication, freeze-thawing, co-extrusion), nanoparticle fusion techniques, and therapeutic functionalization using chemotherapeutics, peptides, cytokines, and photothermal agents. The resulting biomimetic nanosystems demonstrate dual diagnostic and therapeutic (theranostic) potential in diverse fields, including oncology, thrombosis, and inflammatory diseases. We further discuss the development of hybrid platforms, such as red blood cell-platelet membrane combinations, which enhance systemic circulation and targeting efficiency. The review highlights the clinical and translational relevance of platelet membrane-coated nanocarriers, with a focus on their material properties, interaction with biological barriers, and potential for immune escape. Remaining challenges include manufacturing scalability, membrane heterogeneity, and long-term safety. Continued advancement in biointerface engineering and hybridization techniques is expected to expand the applicability of these systems within the broader context of precision nanomedicine.

The ever-growing demand for efficient tumor-targeted delivery of high molecular-weight biomolecules calls for large pore-sized silica nanoparticles with a controlled release feature. Herein, a general organosilica precursor-enlarged micelle (OP-EM) method is introduced for facile synthesis of sub-50 nm large pore-sized hollow mesoporous organosilica nanoparticles (LPHMON). Then an extremely convenient "pore-capping" strategy is proposed to prevent the premature leakage of payloads based on polyphenol-metal coordination chemistry. Following the encapsulation of glucose oxidase (GOx) and surface coating with a tannic acid (TA)-Cu complex, the TA-Cu covered, GOx-loaded LPHMON (LPHMON-GTC) can not only avoid the GOx leakage-induced toxicity, but also go through three-step cascaded catalytic reactions (acidity-activated TA-Cu disassembly, GOx-catalyzed glucose oxidation, and a Cu-mediated Fenton-like reaction), which will facilitate the realization of endogenous tumor-specific cascaded catalytic therapy, promising precise trigger-free treatment of various cancers with minimized side effects.

Correction for 'TPP-coated Mo-doped WO biodegradable nanomaterials with mitochondria-targeting and pH-responsive properties for synergistic photothermal therapy/chemodynamic therapy/chemotherapy' by Yingjuan Ren , , 2025, , 6138-6155, https://doi.org/10.1039/D5BM00833F.

Osteomyelitis, a severe bone infection, poses significant challenges due to antibiotic resistance and limited efficacy of conventional treatments, which often rely on non-degradable carriers with burst antibiotic release. Biodegradable scaffolds with intrinsic antimicrobial functionality offer a promising alternative combining structural support, sustained therapy, and bone tissue regeneration. In this study, novel hydrophobic derivatives of the antibiotic ciprofloxacin-allylciprofloxacin (Cpf-Allyl) and vinylbenzylciprofloxacin (Cpf-VBC) - were synthesized and evaluated as photoinitiators for one- and two-photon polymerization (1PP and 2PP) of star-shaped polylactide (SS-PLA) to obtain scaffolds designed for bone regeneration. Both derivatives retained antimicrobial activity comparable to unmodified ciprofloxacin against key pathogens, including and . Cpf-VBC demonstrated favorable photophysical properties for 2PP: 40% higher absorbance at 263 nm and lower fluorescence quantum yield (8% 10% for Cpf-Allyl), approaching the efficiency of the commercial photoinitiator Bis-b. All photosensitive resins achieved high degrees of conversion (DC ≥ 60%) for the 1PP-method. In contrast, Cpf-VBC-based 2PP scaffolds showed a significantly lower DC (29 ± 4%) compared to both Cpf-Allyl-based and Bis-b-based scaffolds (∼58%). However, the use of Cpf-VBC resulted in increased surface hydrophilicity of the scaffolds, as evidenced by lower water contact angles (62 ± 2°) and a higher polar component of surface energy. All fabricated scaffolds promoted the proliferation of mesenchymal stromal cells and their efficient osteogenic differentiation supported by scaffold mineralization. The scaffolds exhibited topographical and mechanical properties suitable for bone tissue engineering, with a Young's modulus (262-377 MPa) in the range of human cancellous bone.

Correction for 'Artificial testis: a testicular tissue extracellular matrix as a potential bio-ink for 3D printing' by Zahra Bashiri , , 2021, , 3465-3484, https://doi.org/10.1039/D0BM02209H.

Incorporating micelles into polymeric hydrogels offers a powerful route to combine the tuneable mechanical and structural properties of hydrogels with the precise drug-loading and release capabilities of nanocarriers. However, the method of micelle incorporation and its influence on hydrogel performance have yet to be studied in detail. Here, we present a modular strategy to tailor gelatin-norbornene hydrogels by integrating Pluronic® F127 micelles either physically or covalent incorporation using norbornene-functionalised Pluronic (Pl_Nb). Pl_Nb was synthesised Steglich esterification with >95% terminal functionalisation, forming stable, thermo-responsive micelles (2.5-15% w/v) with doxorubicin encapsulation efficiency of ∼80%, comparable to unmodified Pluronic. Micelles were either physically entrapped or chemically integrated into gelatin-norbornene networks bioorthogonal thiol-ene crosslinking. The incorporation route dictated network mechanics and dynamics: chemical crosslinking conferred temperature-dependent behaviour and enhanced stress relaxation compared to physical crosslinking, whereas both incorporation routes reduced stiffness relative to neat hydrogels and slowed drug release compared to direct loading. All hydrogels were cytocompatible, and the released doxorubicin retained its bioactivity, reducing cancer cell viability. These findings establish micelle-hydrogel coupling as a versatile design approach for engineering biomaterials with potential in controlled therapeutic delivery and regenerative medicine.

Respiratory diseases such as COPD, IPF and severe asthma are major causes of death globally, characterized by chronic inflammation and by fibrotic biomechanical remodelling of the lung ECM. However, present treatments focus on relieving inflammation and symptoms and do not address the mechanobiological aspect. This is in great part because the role of mechanobiology in disease progression and aetiology is not well-understood, indicating a need for new investigatory models. Here we introduce a combined biomaterial and 3D-organoid model, based on a hybrid biomaterial-matrix double-network gel, whose mechanical properties are dynamically photocontrolled by the application of light. This combines basement membrane extract (Matrigel) with biocompatible polymer (poly(ethylene glycol)diacrylate), and a low-toxicity photoinitation system. We achieve rapid (<5 min) photoinduced stiffening over the range of remodelled lung tissue (up to ∼140 kPa). Bronchosphere organoids from primary human bronchial epithelial cells, embedded within the hybrid gel, replicate airway physiology and exhibit a dynamic biological response to matrix stiffening. We show that the expression of mucus proteins MUC5AC and MUC5B is biomechanically enhanced over a period of 24-72 h, with in particular MUC5B showing a substantial response at 48 h after matrix stiffening. Mucus hypersecretion is a symptom of respiratory disease, and these results support the hypothesis that biomechanics is a driver of disease aetiology. We combine the photostiffened hybrid matrix gel with organoids from COPD donors, generating an advanced disease model including both cellular and biomechanical aspects. We propose this technology platform for evaluating mechanomodulatory therapeutics in respiratory disease.

The development of effective vaccines against tumor-associated MUC1 (taMUC1) glycopeptide antigens remains a significant challenge due to their poor intrinsic immunogenicity. A key limitation in conjugate vaccine design lies in the structural alterations that occur upon carrier protein functionalization, which can reduce the accessibility of surface-conjugated antigens, ultimately compromising antigen presentation. In this study, we present a semi-synthetic vaccine platform in which taMUC1 glycopeptides are displayed on synthetic cyclopeptide scaffolds-configured either as monovalent or clustered tetravalent platforms-and subsequently grafted onto solvent-exposed amine residues of the CRM protein squaramide linkages. These conjugates were purified under denaturing conditions reverse phase HPLC and evaluated through mouse immunization studies. Despite differences in antigen valency and glycopeptide loading per protein, both conjugates induced comparable levels of antigen-specific IgGs and CD4/CD8 T-cell activation when co-administered with the QS-21 adjuvant. Notably, although antibody titers were similar, post-immunization sera from mice immunized with the tetravalent conjugate plus the QS-21 adjuvant showed enhanced reactivity toward native taMUC1 expressed on MCF7 cancer cells, suggesting improved epitope recognition. These results highlight the impact of scaffold design, antigen display and adjuvantation on vaccine efficacy and establish a promising platform for the development of conjugate vaccines targeting weak tumor-associated antigens.

Atopic dermatitis is a typical chronic inflammatory disease with pathological characteristics of persistent immune activation and oxidative stress. Combined anti-inflammatory and antioxidant treatment can effectively block the inflammatory cascade while reducing oxidative damage. Halloysite nanotubes (HNTs) are the main components of the traditional Chinese medicine "Chishizhi", which shows the medicinal functions of hemostasis and astringency. However, the efficacy of HNTs alone in treating diseases is relatively weak, and their therapeutic effect can be improved by surface modification and drug loading. Herein, CuO-FeO nanoparticles were synthesized on the outer surfaces of HNTs by a hydrothermal reaction. CuO-FeO@HNTs have high SOD and CAT enzyme activities under neutral conditions. Then, the nanozyme-modified HNT powder was prepared into sprayable hydrogels by introduction of sodium alginate (SA) and aloe vera extracts. Cell experiments confirmed that the hydrogel can promote HacaT cell proliferation within 0-200 μg mL concentration. Through the mouse dermatitis model, it was seen that a CuO-FeO@HNTs-SA composite hydrogel has a good therapeutic effect on atopic dermatitis. Compared with the positive drug halcinonide solution, the CuO-FeO nanozyme-incorporated hydrogel showed an enhanced therapeutic effect, which shows promising prospects for the clinical treatment of atopic dermatitis.

Cancer immunotherapy has attracted tremendous attention. To improve the response rate of immune checkpoint inhibitors and tumor antigens in immunosuppressive cancer, the induction of piezoelectric-triggered cancer cell death can increase antigenicity. Herein, we construct a piezoelectric poly(vinyl alcohol) (PVA)/polyvinylidene fluoride (PVDF)/MXene hydrogel loaded with a biomimetic cancer cell membrane (CCM) that incorporates TLR7/8a/anti-PD-L1. The CCM surface proteins act as tumor-specific antigens. Poly(lactic--glycolic acid) (PLGA) is used to enhance the stability and attachment of the MXene. After adding the MXene, the hydrogel exhibits a higher piezoelectric coefficient, greater electrical signal yield with superior stability, and excellent mechanical strength. Ultrasound (US) enhances the piezoelectric effect of the PVA/PVDF/MXene-CCM hydrogel. This is confirmed through reduction and oxidation catalysis reactions. The US-stimulated electrical signal inhibits cancer cells apoptosis induction, endoplasmic stress, and mitochondrial membrane depolarization. It leads to the secretion of danger-associated molecular patterns into the cytoplasm, which promotes dendritic cell maturation and cytotoxic T-lymphocyte infiltration, thereby reversing the immunosuppressive tumor microenvironment. studies show that the hydrogel offers great therapeutic efficacy to control tumor growth due to the combined effects of the piezoelectric effect and immune checkpoint blockade (ICB) therapy. It improves dendritic cell maturation and increases cytotoxic T-cells. Therefore, our work presents a novel piezoelectric hydrogel and new therapeutic strategies with great potential and versatility for treating breast cancers.

Catechol-based surface functionalization has emerged as a powerful strategy for tailoring material properties and enabling diverse applications, owing to its robust adhesive capabilities and broad substrate compatibility. Inspired by mussel foot proteins and popularized by dopamine-derived polydopamine coatings, catechol grafting has evolved into a versatile platform for anchoring molecules of interest (MOI) onto surfaces. This review focuses on the synthetic strategies for direct covalent modification of active compounds-such as polymers, peptides, and small molecules-with catechol moieties, bypassing the limitations of traditional bottom-up and co-deposition approaches. By examining the reactivity profiles of catechol precursors and their coupling chemistries, we aim to provide a comprehensive framework for designing functional coatings with enhanced performance and simplified processing. This work fills a critical gap in the literature by offering practical guidelines for researchers seeking to harness catechol chemistry in advanced material engineering.

Ferroptosis, a regulated cell death pathway characterized by iron dysregulation and lipid peroxide accumulation, has emerged as a pivotal target in the treatment of cancer and other diseases. As a natural iron storage protein in organisms, ferritin (Fn) is involved in regulating intracellular iron homeostasis through processes such as iron transport, storage, and ferritinophagy, which in turn significantly influence the Fenton reaction, making it closely related to the occurrence of ferroptosis. Additionally, due to the unique cavity structure of ferritin nanocages, their excellent biocompatibility and their specific binding ability for the highly expressed transferrin receptor 1 (TfR1) on the surface of tumor cells, ferritin nanocages have been extensively explored in the design and development of drug delivery systems (DDS). Given the above background, this paper reviews the novel mechanisms of ferroptosis and the research advancements in the related diseases and drugs. It further explores the structure and application of ferritin (including DDS design and vaccine development) and emphasizes the construction of DDSs regulating ferroptosis through utilizing ferritin nanocages as carriers or by targeting the disruption of endogenous ferritin, with the expectation of providing a reference for the development of safer and more effective nanoformulations.

Osteochondral (OC) tissue faces significant challenges in defect repair due to its unique gradient characteristics. Bionic gradient scaffolds have been developed to address this issue, whose anisotropic three-dimensional structures can achieve gradual transitions in physical and chemical properties, providing innovative solutions for tissue regeneration. This review first focuses on the multidimensional gradient characteristics of natural OC tissue, including its composition, structure, performance, and metabolism, and provides an in-depth discussion of its significance for the design of biomimetic scaffolds. Second, it summarizes the current research progress on the construction strategy of gradient scaffolds. On this basis, this review innovatively proposes a systematic interface optimization strategy for discrete gradient scaffolds and summarizes the latest research progress on the gradient characterization and controllability of continuous gradient scaffolds. Finally, based on the current advances of research, this paper evaluates the main challenges facing this field and reviews the prospects in future development directions, providing new theoretical perspectives and technical routes for OC tissue engineering research.

Targeted protein degradation (TPD), a strategy currently used for treating diseases, can selectively degrade specific proteins, thereby circumventing drug resistance. Nevertheless, over 80% of the pathogenic proteins linked to human diseases, including membrane proteins, are not accessible to conventional methods. Aptamers, which are nucleic acid molecules with high affinity and specificity, are chosen from vast libraries of random sequences through screening techniques. These aptamers can effectively recognize and bind to disease-related membrane proteins, such as those associated with cancer, cardiovascular diseases, and inflammation. Consequently, aptamer-based TPD technology uses these aptamers to deliver target membrane proteins into cells, promoting their degradation and allowing for the specific elimination of pathogenic proteins. This technology showcases significant progress in overcoming the limitations of traditional small molecule inhibitors and in targeting proteins previously considered "undruggable". In this review, we provide an overview of the latest advancements in aptamer-based TPD technology research.

Driven by changes in modern lifestyles and growing health awareness, obesity has become a significant global public health concern. It not only impacts physical appearance and psychological well-being but also constitutes a significant risk factor for chronic diseases, including cardiovascular disorders, diabetes, and hypertension. Microneedle-based delivery of anti-obesity drugs, a novel and non-invasive technology, has attracted considerable attention in recent years. This review aims to provide a comprehensive overview of microneedle types, materials, fabrication techniques, recent advancements in their application to anti-obesity drug delivery, underlying mechanisms of action, and therapeutic outcomes. The challenges and future directions of microneedle-based weight loss strategies are also discussed. As an innovative approach to obesity management, microneedle therapy holds promising prospects for application and market potential, offering a safer, more effective, and convenient solution for individuals with obesity.

Nanoarchitectured molybdenum oxides (MoO) have emerged as promising artificial enzymes, capable of mimicking a broad range of enzymatic activities, including oxidase, peroxidase, catalase, and sulfite oxidase, owing to their unique physicochemical properties such as variable oxidation states, tunable electronic structures, and pH-responsive biodegradability. In addition, MoO-based systems demonstrate strong photoresponsiveness, enabling the synergistic integration of enzymatic catalysis with photothermal (PTT) or photodynamic (PDT) therapies under near-infrared (NIR) irradiation. Their excellent biocompatibility and biodegradability further highlight their potential for biomedical applications. This review provides a comprehensive overview of recent advances in the design, synthesis, and bioapplications of MoO nanozymes, with an emphasis on their structural versatility and multifunctional therapeutic capabilities. Through strategies such as defect engineering, surface functionalization, and heteroatom doping, the enzyme-mimicking activities of MoO nanozymes can be finely tuned, enabling outstanding performance in biosensing, antitumor and antimicrobial therapies, and antioxidation. Finally, the review outlines the prospects and key challenges in translating these innovative nanoplatforms into clinical applications.