Latest ArticlesMetal-based nanomedicine, which involves nanoparticles (NPs) composed of metals such as gold, silver, iron, and platinum, has emerged as a promising approach in drug delivery, cancer therapy, imaging, and diagnostics. This review systematically examines a variety of metal-containing NPs (MNPs), including elemental metal NPs, metal oxides, metal-organic frameworks, nanozymes, and up-conversion NPs, highlighting their unique physicochemical properties and biomedical applications. The biological functions of MNPs, particularly in drug delivery, imaging, and therapeutic contexts, are critically discussed. Key engineering strategies aimed at optimizing targeted delivery, drug loading, responsive release, and biocompatibility are explored, with a focus on enhancing clinical outcomes. Recent advances underscore the potential of MNPs in innovative applications such as liquid biopsy, tumor imaging, chemotherapy, immunotherapy, physical therapy, and nanozyme-mediated treatments. Despite promising developments, clinical translation remains hindered by challenges such as toxicity, scalability, and regulatory hurdles. This review concludes with an outlook on future directions for MNPs, emphasizing their potential to revolutionize disease diagnosis and treatment through innovative biomaterial design and engineering.
Calcitonin (CT), a 32-amino acid polypeptide drug, is crucial in regulating calcium homeostasis and inhibiting osteoclast activity. CT is primarily administered via injections and nasal sprays. However, injections usually suffer from poor patient compliance, while nasal sprays may cause side effects such as epistaxis, rhinitis, and nasal mucosal ulcers, coupled with low bioavailability. Deep eutectic solvents (DESs), formed by hydrogen-bond donors and acceptors, have shown potential in overcoming intestinal permeability barriers and facilitating the oral delivery of peptide drugs. Herein, we developed an intestinal drug delivery system for CT using DESs, which is expected to facilitate the subsequent development of oral preparations. We first prepared and characterized DESs with different stoichiometric ratios of choline (Ch) and geranate (Ge), followed by the investigation of the interaction between CT and Ch-Ge-based DESs (CAGE). Intestinal transport studies revealed that CAGE significantly promoted the jejunal absorption of CT-CAGE 1:2 (Ch and Ge in a 1:2 ratio), exhibiting the most pronounced pro-permeability effect. In vivo pharmacokinetic and pharmacodynamic results indicated that, compared with the aqueous CT solution, the CT-CAGE formulation increased bioavailability to 3.53%, with a significant hypocalcemic effect. In vitro studies further demonstrated that CAGE increased the transmembrane transport and membrane permeability of CT. The pro-permeability mechanism of CAGE may be related to the opening of tight junctions between intestinal cells and the improvement of paracellular transport efficiency. This DES-based drug delivery system offers a novel and promising approach for the oral delivery design of CT, addressing the limitations of administration routes.
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, frequently presenting with metastatic progression to the liver. A hallmark of CRC is redox dysregulation, characterized by elevated levels of γ-glutamyl transferase (GGT) and hypochlorite (ClO−). However, bioluminescent probes capable of simultaneously detecting GGT and ClO− for sensitive in vivo CRC diagnosis and ex vivo fecal analysis remain lacking. Herein, we report a novel dual-locked bioluminescent probe, GClO-luc, designed for the simultaneous detection of GGT and ClO− in CRC and stool testing. GClO-luc remains silent until sequentially activated by GGT and ClO−, generating a turn-on bioluminescence response in both aqueous solution and fLuc-transfected CT26 cells. Notably, this probe enabled real-time visualization of small tumors in both CRC and colorectal cancer liver metastasis (CRLM) mouse models, achieving high signal-to-background ratios of 65:1 and 41:1, respectively. Moreover, GClO-luc was successfully applied to fecal analysis, showing significantly higher bioluminescence intensity in the feces from CRC and CRLM mice. These findings demonstrate that GClO-luc represents a powerful dual-responsive diagnostic tool for cancer diagnosis and stool examinations.
Inflammatory bowel disease (IBD) exhibits pathological heterogeneity driven by multifactorial origins and patient variability, posing therapeutic challenges due to divergent immune microenvironment dynamics. Notably, neutrophils and macrophages showed prominent heterogeneity in IBD patients and underwent different reprogramming during the acute and chronic inflammatory phases. To address this pathological complexity, an orally administered TH@PVP-gel system integrating tanshinone IIA (Tan) and hemin (Hem) was engineered to address the heterogeneity of IBD pathology with the aim of achieving multi-targeted modulation of IBD. TH@PVP-gel specifically promoted neutrophil apoptosis and facilitated macrophage M2 polarization in the inflamed environment of the colon, targeting inflammatory heterogeneity and remodeling the inflammatory environment. In addition, the TH@PVP-gel efficiently scavenged reactive oxygen species (ROS), inhibited the death of colonic epithelial cells, and restored the intestinal barrier. Ultimately, the TH@PVP-gel demonstrated excellent therapeutic efficacy in both acute and chronic colitis, providing a potential strategy for the broad-spectrum treatment of IBD.
The combination of sonodynamic therapy (SDT) and immunotherapy exhibits potent anticancer efficacy. However, most sonosensitizers produce reactive oxygen species (ROS) with low efficiency under ultrasound (US). Chemotherapy-induced immunogenic cell death (ICD) is also plagued by toxic side effects, suboptimal efficacy, and immune escape. Herein, we developed a cancer therapy platform based on a sonosensitizer, iron porphyrin (Fe(Ⅲ) meso-tetra(4-carboxyphenyl)porphine chloride, FeTCPPCl), which self-assembles into a hydrogen-bonded organic framework (PHOF-1). This platform enables precise activation and spatiotemporal controlled release of prodrugs, thereby inducing ICD efficiently and safely. Specifically, PHOF-1 bioorthogonally activates the doxorubicin prodrug (pro-DOX) in situ, synergizing with sonodynamic immunotherapy. This strategy, which combines SDT with in situ prodrug activation, minimizes drug side effects and maximizes therapeutic effects. Additionally, this system activates the metformin (Glucophage) prodrug (pro-MET), with ATP depletion leading to upregulated adenosine monophosphate activated protein kinase (AMPK) expression, increased programmed death-ligand 1 (PD-L1) degradation, and reversal of tumor immunosuppression. Remarkably, SDT combined with bioorthogonal in situ immune activation represents a novel approach to enhance cancer immunotherapy. This synergy effectively converts "cold" tumors into "hot" tumors by promoting ICD and reducing PD-L1 expression, thereby improving immunotherapy efficacy. The integration of SDT and bioorthogonal chemistry offers a controllable therapeutic strategy with reduced immune-related adverse effects, providing a promising avenue for safer and more effective cancer immunotherapy through the induction of adaptive antitumor immunity.
Rapid hemostasis is a paramount issue in tissue wound repair treatment. Currently, hydrophilic hemostatic materials are favored for their absorption concentration capabilities in achieving swift hemostasis. However, the subsequent adherence of these materials to the wound presents another challenge, impacting the overall therapeutic outcome. Here, we reported a flexible electrospinning membrane (75D-P) composed of polyacrylonitrile (PAN) and diatom biosilica (DB), which integrated the submicron-sized pores of fiber membranes with the hierarchical porous structure of DB. It exhibited weak interfacial hydrophobicity, enabling rapid plasma protein adsorption capacity and accelerating blood coagulation at the material interface. The clotting time of kaolin commercial hemostatic agent-QuikClot® (QC) was 200 s, and that of 75D-P was 100 s, with the minimum tissue adhesion (0.06 N). Importantly, in the rabbit injury models, the dosage of the 75D-P was far below that of the QC group, yet it maintained comparable clotting time (about 400 s) and blood loss (4 g). We have integrated DB and PAN in electrospinning membrane could achieve a distinct water repellenting separation effect on blood components, promoting efficient interfacial blood coagulation. These offer insights into facilitating the blood clots formation at interfacial, thereby mitigating excessive material blood absorption and tissue adhesion.
Chronic cutaneous wounds such as diabetic foot and pressure ulcers are increasing worldwide and remain difficult to manage. Conventional approaches are hindered by prolonged healing and antibiotic resistance, highlighting the need for advanced biomaterial strategies. Thus, the production of advanced biomaterials for efficient wound healing has become of special urgency. Mesoporous silica (MS), with its specific features of exceptional biocompatibility, easily tunable pore architectures, and multifunctional surface functionalization, has emerged as a promising choice in such applications. The review systematically overviews the most recent advances in the wound healing application of MS, with its participation in drug delivery, controlled inflammation, modulation of immune response, tissue regeneration, and angiogenesis. Synthesis methods, surface functionalization techniques, and incorporation of advanced technology such as stimulus responsive systems and multifunctional composites are also extensively reviewed. Furthermore, this review critically examines the key barriers to the clinical translation of MS, including long-term biosafety, immune compatibility, and scalable manufacturing. Overcoming these challenges is crucial for harnessing its full potential in next-generation wound healing. By integrating MS with precision medicine and emerging biomedical technologies, this review highlights its transformative role in advancing personalized wound care and regenerative medicine.
Synergistic strategy of cationic antibacterial and nanoparticle mediated photothermal conversion provides new opportunities to address bacterial infections. However, the conventional post-modification and lack of precise structural regulation, leads to the complexity of operation and unsatisfying synergistic effect on antibacterial performance. To address these challenges, herein, a novel "selective extraction and domain-restricted growth" approach has been proposed to successfully synthesize quaternized mesoporous silica nanosphere (QMSN) encapsulating gold nanorods (GNRs) inside the pore channel (GNRs@QMSN) for the treatment of bacterial infected diabetic wound. The strategy exhibits extensive convenience, enabling the ultra-uniform microporous core-mesoporous shell structure with positive charges. Most importantly, GNRs@QMSN demonstrated an excellent photothermal conversion efficiency up to 63.73%, due to the unique pore-domain-limited effect. Under the synergistic effect of positive charge surface for enhanced bacteria adhesion, intrinsic antibacterial quaternization and GNRs-mediated photothermal conversion, GNRs@QMSN exhibited excellent antibacterial and antibiofilm performance in vitro. The feasibility of GNRs@QMSN was further validated in a mouse diabetic wound infection model. This novel QMSN encapsulating GNRs is expected to be a promising paradigm for bacterial infected wound healing.
Aqueous Zn//MnO2 batteries with Mn2+/MnO2 conversion reactions are highly promising due to their high redox potential and low cost. Typically, the conversion of Mn2+/MnO2 occurs at a strong acidic environment to ensure sufficient proton participation in the reaction, which will lead to Zn anode corrosion and electrolyte decomposition. Here, an acid-free mild electrolyte with Al2(SO4)3 as the additive to trigger Mn2+/MnO2 conversion through the hydrolysis of Al3+. This approach not only provides protons to enhance the two-electron transfer reaction but also utilizes the electrostatic shielding effect of Al3+ effectively inhibiting the formation of Zn dendrites and protecting the Zn anode. As a result, the assembled aqueous Zn//MnO2 battery exhibits high discharge voltage (1.6 V), long cycling stability (1900 cycles without decay) and excellent rate performance. Meanwhile, the anode-friendly electrolyte facilitates stable Zn plating/stripping and high Coulombic efficiency. This work proposes an effective strategy for enabling the two-electron process of MnO2 in mild aqueous Zn batteries.
Vitiligo is a chronic autoimmune disorder characterized by progressive melanocyte loss. Conventional narrowband ultraviolet B (NB-UVB) phototherapy for vitiligo faces limitations due to reactive oxygen species (ROS)-induced phototoxicity and insufficient melanocyte regeneration in chronic applications. In this study, we propose a differential dual-release bilayer microneedle loaded with two natural plant-derived polyphenols nanoparticles, which integrates rapid antioxidant defense and sustained melanogenic reprogramming for precision vitiligo phototherapy. The upper layer, composed of hyaluronic acid (HA), encapsulates curcumin-fructose self-assembled nanomicelles (CF NMs) for rapid ROS scavenging (68.50% within 15 min), to prevent photodamage and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammation. The lower gelatin methacryloyl (GelMA) hydrogel layer sustains the release of psoralen-loaded melanin-mimetic mesoporous polydopamine nanoparticles (PMPN), which persistently inhibits the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and reduces autophagy-induced apoptosis, while enhancing tyrosinase activity (0.47-fold increase) to promote melanogenesis. In monobenzone-induced vitiligo mice, the CF/HA-PMPN/GelMA-MNs combined with NB-UVB demonstrated superior outcomes with 80.55% repigmentation at day 14 (vs. 25.90% in NB-UVB alone). This "rapid defense-sustained regeneration" paradigm provides a clinically translatable strategy to enhance efficacy and safety in vitiligo phototherapy.
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