Journal of Materials Chemistry B最新文献

The demand for safe, effective, and multifunctional magnetic resonance imaging (MRI) contrast agents (CAs) continues to drive the search for gadolinium-free alternatives. Here, we report the development of BVR-19-Mn, a novel, hydrolytically stable metal–organic framework (MOF) constructed from manganese (Mn(II)) and the amino acid L-cystine via a green, aqueous, room-temperature synthesis. BVR-19-Mn exhibits a high r₁ relaxivity of 4.98 mM⁻¹ s⁻¹ in water at 3 T and 25 °C, outperforming clinically approved gadolinium-based CAs such as Dotarem® under identical conditions. The enhanced relaxivity arises from a dense framework of Mn(II) centers, efficient water accessibility to internal pores, and favorable rotational dynamics inherent to its crystal structure. Importantly, BVR-19-Mn also demonstrates catalase-like activity, rapidly decomposing hydrogen peroxide into molecular oxygen, offering a mechanism to relieve tumor hypoxia. In vitro cytotoxicity and in vivo developmental zebrafish studies confirm biocompatibility across clinically relevant concentration ranges, with low toxicity observed at high dosing concentrations. Collectively, our findings position BVR-19-Mn as a high-performance MRI CA, introducing a sustainable, multifunctional platform for precision biomedical imaging.

Periodontitis and peri-implantitis, driven by dysbiotic biofilms and aberrant host immune responses, lead to pathological inflammation and alveolar bone resorption. Conventional therapies targeting microbial debridement and inflammation control often fail to achieve predictable tissue regeneration. Recent advances in biomaterial science have introduced intelligent biomaterials as transformative tools for precision treatment and functional tissue restoration. These bioengineered scaffolds dynamically interact with the pathological microenvironment through programmable responses to external or endogenous stimuli, enabling spatiotemporal control over immunomodulation, antimicrobial delivery, and osteogenic differentiation. This review aims to comprehensively summarize the progress of intelligent biomaterials in the treatment of periodontitis and peri-implantitis, highlighting their potential for providing targeted and controllable therapy, providing guidance for the development of clinically translatable strategies in future periodontal regenerative medicine, and underscoring multifunctionality, adaptive responsiveness, and enhanced control over efficacy. It systematically reviews the mechanisms, design strategies, advantages and limitations of intelligent biomaterials in addressing the complex pathophysiology of periodontitis and peri-implantitis. By integrating multifunctional responsiveness with clinical applicability, these systems offer unprecedented potential to bridge antimicrobial therapy and regenerative dentistry.

Ir(III)-based metallo-anticancer complexes offer promising therapeutic strategies with their efficacy fine-tuned through structural modifications, leveraging multitargeted mechanisms of action to reduce resistance compared to traditional chemotherapeutics. Herein, we report a photoactive Ir(III)-complex [Ir-biotin] designed with an ion-chelating ancillary ligand to disrupt copper homeostasis and simultaneously induce oxidative stress, aiming to overcome chemotherapeutic drug-resistance in pancreatic cancer. The complex features a nonsymmetrical polytopic ligand covalently linked to phenanthroline and imidazole-quinoline fragments, with a biotin tag for targeted delivery and an open N^N-coordination site for cellular ion interactions. Ir-biotin exhibits potent micro- to nanomolar-level therapeutic efficacy against MIAPaCa-2 and PANC-1 cells under dark and light conditions. We observed that ferroptosis-inducing Ir-biotin significantly downregulated glutathione peroxidase 4 (GPX4) expression, leading to increased lipid peroxidation (LPO) accumulation. Collectively, mechanistic investigations reveal that Ir-biotin translocates into the mitochondria, preferentially coordinates with mitochondrial Cu-ions, and induces a significant increase in reactive oxygen species (ROS), lipid peroxidation (LPO) in the cell membrane, and photoregulated oxidase-mimicking activity. Ir-biotin synergistically triggers apoptosis-linked ferroptosis and therefore represents a promising candidate for overcoming drug resistance via chemo-photodynamic tumor therapy.

In cancer combination therapy, micro-robot systems that integrate multiple therapeutic functions have emerged as a key direction for overcoming the limitations of traditional treatments. This study proposes a magnetic thermosensitive hydrogel capsule micro-robot that combines both drug-targeted delivery within blood vessels and local magnetic hyperthermia therapy. By introducing acrylamide and sodium alginate to modify the poly(N-isopropyl acrylamide) hydrogel system, the thermal response characteristics and drug-loading capacity of the micro-robot carrier are optimized. A multi-coaxial co-flow microfluidic chip is employed to achieve the directed encapsulation of Fe₃O₄ nanoparticles and the rapid, controlled preparation of single-core and core–shell structured spherical micro-robots. The core–shell structure enables the simultaneous loading of hydrophilic and hydrophobic drugs. Under the influence of a high-frequency alternating magnetic field, the local temperature around the micro-robot increased from 21 °C to 42 °C within 4 minutes, successfully triggering the phase transition contraction of the hydrogel and releasing the drug while also reaching the temperature threshold for thermal therapy. Additionally, this study established a visual feedback, magnetically driven system, with the micro-robot achieving a maximum movement speed of 3.47 mm s⁻¹ under a magnetic field strength of 7.4 mT, thereby realizing millimeter-level positioning accuracy and complex curve trajectory tracking in vascular microchannels that simulate a blood environment. Experimental results indicate that the prepared multimodal hydrogel capsule microrobots possess excellent targeted movement capabilities, meeting the functional requirements for a synergistic “thermotherapy-chemotherapy” treatment, and demonstrate potential application in the development of low-toxicity, high-efficiency tumor combination therapy.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by inadequate drug delivery to tumor sites, insufficient immune activation, and poor response to conventional monotherapies. To overcome these limitations, we developed a pH and near-infrared (NIR) responsive nanoplatform (DOX@MPDA-TPP@HA) by encapsulating doxorubicin (DOX) into mesoporous polydopamine (MPDA) nanoparticles functionalized with triphenylphosphonium (TPP) and hyaluronic acid (HA) to achieve mitochondrial and CD44 dual-targeting. This system enables combined chemotherapy and photothermal therapy, while simultaneously promoting immunogenic cell death and enhancing antitumor immunity. In vitro and in vivo experiments demonstrated that the nanoplatform exhibits acid and NIR-triggered drug release, efficient photothermal conversion, and enhanced cellular uptake in tumor cells. Treatment significantly increased calreticulin exposure and high-mobility group box 1 (HMGB1) release, both recognized as hallmarks of immunogenic cell death. Flow cytometry revealed a marked increase in the maturation of CD11c⁺CD80⁺CD86⁺ dendritic cells in tumor-draining lymph nodes, elevated intratumoral CD8⁺ cytotoxic T lymphocyte infiltration, and a reduction in CD4⁺Foxp3⁺ regulatory T cells. Enzyme-linked immunosorbent assay (ELISA) confirmed the elevated secretion of proinflammatory cytokines including interleukin-6, interleukin-12, tumor necrosis factor-alpha, and interferon-gamma, suggesting immune reprogramming of the tumor microenvironment. Collectively, these results demonstrate that DOX@MPDA-TPP@HA effectively integrates chemotherapy, photothermal ablation, and immune modulation, offering a promising therapeutic strategy for the treatment of hepatocellular carcinoma.

Photothermal therapy (PTT) represents a non-invasive therapeutic modality with considerable potential for tumor ablation. However, the complex tumor microenvironment (TME) presents substantial challenges to conventional PTT monotherapy. In this study, we developed a nanomedicine (Fe₃O₄@GOx@PDA) designed to synergistically eradicate tumor cells by integrating PTT with starvation therapy and ferroptosis induction. Glucose oxidase (GOx) catalyzes the oxidation of intratumoral glucose to gluconic acid and hydrogen peroxide (H₂O₂). Simultaneously, the resultant H₂O₂ facilitates intracellular Fenton-like reactions, generating reactive oxygen species (ROS) that trigger lipid peroxidation. Furthermore, Fe²⁺ ions liberated within the TME react with H₂O₂via a Fenton-like reaction to produce abundant ROS. This ROS surge stimulates macrophage polarization towards the M1 phenotype, thereby further suppressing the proliferation and metastatic potential of colorectal cancer (CRC) cells. This multimodal therapeutic strategy, leveraging Fe₃O₄@GOx@PDA, demonstrates potent synergistic antitumor efficacy coupled with favorable biosafety, presenting a promising therapeutic approach for clinical colorectal cancer management.

Messenger RNA (mRNA) vaccines face core challenges including low-delivery efficiency and immunogenicity, limiting their wide-ranging applications in infectious disease prevention and cancer therapy. Lipid nanoparticles (LNPs), the most clinically validated non-viral delivery platform, address these challenges by encapsulating and protecting mRNA, promoting cellular uptake, and mediating endosomal escape. mRNA-LNP vaccines leverage a “rapid design + flexible production” advantage, decisively demonstrated by the success of COVID-19 vaccines such as BNT162b2. This review systematically analyzes mRNA-LNP vaccine development, focusing on core optimization strategies: (1) mRNA sequence engineering (nucleoside modification and UTR/poly(A) tail optimization) to enhance stability and translation efficiency; (2) LNP formulation (component ratio optimization, SPOT strategies, etc.) to modulate immune responses and enable organ targeting; and (3) LNP surface functionalization (with small molecules, peptides, and antibodies) for precise specific cell or organ targeting. Although multiple candidate vaccines for infectious disease prevention and cancer treatment have entered clinical trials, their clinical translation is still limited by insufficient targeting accuracy, potential immunogenicity and toxicity, and the challenge of universal delivery systems. Future breakthroughs require the integration of multidisciplinary innovations, focusing on the development of degradable lipids and novel targeting ligands to improve delivery precision, the application of more biocompatible polymers (such as pSar and POx) to replace PEG to enhance safety, and the use of artificial intelligence (AI) to accelerate LNP formulation design and performance prediction. This review summarizes the key optimization strategies and clinical progress and explores future directions to overcome the existing bottlenecks and promote mRNA-LNP technology as the cornerstone of next-generation precision medicine.

Organizing enzymes on self-assembled protein cages offers a promising strategy to replicate nature's catalytic efficiency. However, most existing studies have focused on the functionalization of one-component protein cages. Here, we present a two-component protein cage scaffold, I5232_STNT, engineered with orthogonal SpyTag/SpyCatcher (ST/SC) and SnoopTag/SnoopCatcher (NT/NC) systems for flexible enzyme recruitment. This addressable scaffold enables programmable co-localization of distinct proteins containing cognate bioconjugation domains, both in vitro and in living cells, as demonstrated using fluorescent protein pairs. Moreover, we show that cargo proteins can be loaded onto the protein cages both before and after cage formation. By integrating a membrane-targeting peptide, we redirected the cytosolic enzyme Idi (isopentenyl diphosphate isomerase) to the Escherichia coli membrane, positioning it proximally to the downstream lycopene pathway enzyme CrtE. This spatial organization resulted in a 4.0-fold increase in lycopene production, demonstrating the scaffold's capacity to enhance metabolic flux through substrate channeling. Our modular platform provides a versatile tool for constructing spatially organized multi-enzyme assemblies, with broad applicability in synthetic biology and metabolic engineering.

The efficient delivery of nucleic acids (NAs) remains a major challenge in gene therapy due to their poor stability and limited cellular uptake. Even though non-viral vectors have been pivotal to overcoming some of these challenges, significant barriers, such as intracellular digestion of NAs and limited endosomal escape, still remain. Here, we developed novel stimuli-responsive lipoplexes integrating a 2-hydroxychalcone-based cationic amphiphile (C_nNCh, with 4 or 6 carbons in their alkyl chains, n = 4 or 6) and monoolein (MO). This combination leverages the photoisomerization and pH-sensitivity of chalcone derivatives, along with the fusogenic capabilities of MO, to achieve enhanced transfection efficiency via light irradiation. To reach this goal, we first assessed the cytotoxicity of the cationic amphiphiles in healthy and tumor cells. We then prepared mixtures with varying C_nNCh/MO molar ratios, yielding net cationic vesicles with long-term colloidal stability. Subsequently, NAs were efficiently compacted into lipoplexes at N/P ratios (positively charged nitrogen/negatively charged phosphate) higher than 1, attaining near-complete compaction. Light and pH stimuli induce the formation of the expected products, but without compromising lipoplex stability or activating premature NA release. Vesicles with different C_nNCh/MO molar ratios do not induce the loss of viability of normal fibroblasts for concentrations up to 50 µM. Crucially, siRNA-lipoplex mixtures having C₄NCh/MO molar ratios of 1/1 and 2/1 (N/P = 6) achieve significant GFP knockdown after irradiation, indicative of successful siRNA delivery and biological effects. Using biomimicking endosomal membranes, we show that photoactivation enhances membrane fusion, suggesting a mechanism entailing light-mediated endosomal escape. Our study provides proof-of-concept for a “light-switch” mechanism offering precise spatiotemporal control over gene silencing, a highly desirable feature in therapeutic applications.

Nanozymes engineered nanomaterials with enzyme-like catalytic activity—have emerged as cost-effective and stable alternatives to enzymes. However, their broad substrate range and lack of specificity limit their utility in precision biosensing. To overcome this, molecularly imprinted polymers (MIP) have been integrated with nanozymes, forming hybrid nanozyme@MIP systems that combine catalytic efficiency with molecular recognition. These materials exhibit enhanced selectivity and sensitivity, enabling their application in diverse biosensing platforms, including colorimetric, fluorescence, and electrochemical assays for the detection of drugs, pollutants, and disease biomarkers. This review critically examines recent advances in the design, synthesis, and application of nanozyme@MIP composites. This review provides a timely and comprehensive analysis of molecularly imprinted nanozymes, presenting a viable alternative to conventional enzyme-based systems. It bridges a critical gap by detailing design strategies, catalytic mechanisms, and biosensing applications. Its clarity, depth, and interdisciplinary relevance make it a valuable resource for advancing research and practical applications in this emerging field. We explore various imprinting strategies, catalytic mechanisms, and assay formats, while highlighting their advantages over conventional biosensors, such as improved stability, reusability, and cost-effectiveness. Key challenges are addressed, including the trade-off between selectivity and catalytic activity, non-specific adsorption, and the predominance of peroxidase-like mechanisms. Special attention is given to performance in complex matrices, scalability of synthesis, long-term stability, and biocompatibility. Furthermore, we discuss the need for standardized protocols to ensure reproducibility and comparability across studies and propose design principles to optimize MIP layer properties for enhanced performance. By integrating recent literature and comparative analyses, this review provides a comprehensive framework to guide future research and industrial translation of nanozyme@MIP-based biosensors for diagnostics, environmental monitoring, and point-of-care applications.