Employing neutrophils (NEs) as endogenous moving gears offers a promising strategy for crossing the blood-brain barrier (BBB) in the treatment of central nervous system (CNS) malignancies such as glioblastoma (GBM). However, in vivo hitchhiking efficiency of NEs is severely limited by spontaneous formation of a nonspecific protein corona. Here, we present pathogen-mimetic liposomes (PM-Lipo) that enable efficient and precise NEs hitchhiking by programming the in vivo protein corona. PM-Lipo is rationally engineered to preferentially enrich complement 3b (C3b) and inactivated C3b (iC3b), thereby recapitulating endogenous complement opsonization and promoting complement receptor 3 (CR3)-mediated recognition by activated NEs. This effect arises from the synergistic integration of two functional lipids that activate distinct complement pathways, triggering a proteolytic cascade with positive feedback to amplify C3b/iC3b deposition. Our results demonstrate that PM-Lipo achieved >85% targeting efficiency toward activated NEs, enabling hitchhiking-mediated transport across the BBB, with 8.94% of the administered PM-Lipo successfully penetrating the brain, leading to marked tumor suppression and more than a twofold extension in median survival. Our research establishes a protein corona programming strategy to harness endogenous immune cells for targeted drug delivery, offering a broadly applicable paradigm for precision nanomedicine in CNS malignancies.

Lipid nanoparticles (LNPs) represent the most clinically advanced platform for RNA delivery and have enabled major breakthroughs in vaccines and gene therapies. However, their broader application is still limited by inefficient extrahepatic delivery, immunogenicity, and insufficient control over tissue‐ and cell‐specific targeting. This review provides a mechanistic overview of recent advances in LNP engineering for RNA therapeutics. We systematically analyze how key physicochemical parameters and structural elements, including ionizable lipid headgroups, linkers, tail architectures, helper lipids, cholesterol analogs, and surface modifications, govern biodistribution, endosomal escape, immunogenicity, and therapeutic efficacy. Emerging targeting paradigms, encompassing ligand‐mediated active targeting, formulation‐driven intrinsic targeting, and administration‐route optimization, are discussed with a focus on tumor and immune organ delivery. In addition, we highlight enabling methodologies such as DNA barcoding, multiplexed in vivo screening, and data‐driven lipid design that are reshaping LNP discovery. Finally, translational challenges and future directions for precision RNA delivery in cancer therapy are discussed, with an emphasis on how rational LNP design can be leveraged to overcome cancer‐specific barriers such as tumor heterogeneity, stromal constraints, and the immunosuppressive tumor microenvironment (TME).

Exploring two-dimensional semiconductors with mechanical flexibility, auxetic behavior, and tunable physical properties is of great significance for the development of flexible electronics and optoelectronic devices. In this study, eight square-lattice monolayers MX2 (M = Si, Ge, Sn, Pb; X = Se, Te) were systematically studied by first-principles calculations. After thorough assessments of thermodynamic, dynamical, mechanical, and thermal stability, SiSe2 and SnSe2 were identified as stable candidates. These two monolayers exhibit maximum in-plane Young’s moduli as low as 76.55 and 45.08 N/m, respectively, and negative in-plane Poisson’s ratios of -0.05 and -0.045, indicating mechanical softness and intrinsic auxetic behavior. SiSe2 and SnSe2 were found to be indirect-band-gap semiconductors with band gaps of 2.08 and 2.14 eV, respectively, which can be effectively tuned by strain engineering. Carrier transport analysis indicates that SiSe2 and SnSe2 exhibit opposite transport preferences, with SiSe2 favoring holes (37.46 cm2V-1s-1) and SnSe2 favoring electrons (105.61 cm2V-1s-1). Moreover, optical absorption spectra of both monolayers demonstrate strain-induced redshifts and polarization-dependent anisotropy under uniaxial strain, whereas biaxial strain preserves in-plane isotropy and causes pronounced redshifts. These findings indicate that SiSe2 and SnSe2 monolayers are promising two-dimensional candidates for flexible electronic and strain-modulated optoelectronic applications.

Clinical translation of sonodynamic therapy for hepatocellular carcinoma is limited by a safety-efficacy paradox: sonosensitizer activation in healthy tissues poses risks, while tumor efficacy is constrained by hypoxia and redundant antioxidant defenses. To resolve this, dual-switchable core-shell nanoparticles were engineered. Under physiological conditions, a carboxymethyl chitosan shell and a peptide radical scavenger keep the nanoparticles inert, ensuring systemic safety. In the acidic tumor microenvironment, the shell disassembles, and ultrasound exposure triggers a coordinated therapeutic cascade. The linear dumbbell‑shaped piezoelectric core, barium titanate‑gold‑barium titanate heterojunction, generates oxygen, alleviating tumor hypoxia, and simultaneously produces oxyradicals, enabled by a record piezopotential of 4.12 V and its inherent direct water‑splitting capability. Two inhibitors are released to block the AMP‑activated protein kinase and nuclear factor erythroid two-related factor 2 antioxidant pathways, disabling cellular defenses and amplifying oxidative damage. This integrated strategy induces ferroptosis, mitochondrial dysfunction, DNA damage, and immunogenic cell death, as validated by physicochemical characterization, multi-omics, and in vivo studies. In subcutaneous tumor models, inhibition rates reached 98.7% in immunocompetent mice and 91.9% in T‑cell‑deficient mice, with excellent safety. This work establishes a therapeutic paradigm reconciling systemic safety with potency, offering a translatable strategy for HCC.

In vivo genetic engineering of T cells could overcome the logistical, biological, and safety challenges of ex vivo modification, but effective and safe delivery systems remain limited by a lack of cellular specificity. Here, we developed aptamer-functionalized lipid nanoparticles (LNPs) for targeted mRNA delivery to CD4 + T cells, employing both a validated CD4-binding aptamer (Apt62) and novel aptamers generated using our proprietary transformer-based AI language model, AptaBLE. LNPs formulated with ionizable lipid SM102 or MC3 and conjugated with aptamers at controlled densities were physiochemically characterized and assessed for binding, in vitro transfection, in vivo biodistribution, and safety evaluation. Aptamer-functionalized LNPs demonstrated selective nanomolar binding to recombinant CD4, achieved enhanced transfection of CD4⁺ versus CD4- T cells in vitro, and significantly enriched mRNA delivery to immune-rich tissues in vivo, achieving up to 70-fold spleen signal enhancement with SM102 formulations Compared to non-targeted controls, while maintaining suitable safety profiles. Overall, these findings demonstrate aptamer-functionalized LNPs, augmented by AI-guided aptamer design, as a tunable, non-immunogenic platform for in vivo T-cell engineering.

The quest for sustainable energy transition has intensified the demand for lithium extraction from salt-lake brines, necessitating advanced membranes for high-efficiency Li+/Mg2+ separation. Integrating porous frameworks and two-dimensional (2D) scaffolds has shown promise for fabricating ion-permselective membranes, but is hampered by poor processability. Here we transform crystalline frameworks into porous liquids (PLs), and embed them within graphene oxide (GO) laminates to engineer an ultrathin and defect-free GO/PLs membrane. Discrete porous guests are uniformly confined within 2D nanofluidic channels mediated by a sterically hindered solvent. The GO/PLs membrane exhibits ultrahigh Li+ permeance (0.75 mol m-2 h-1) and exceptional Li+/Mg2+ selectivity (154.4) by regulating ion dehydration and ion-to-channel interactions. Efficient lithium extraction from simulated brine is demonstrated, reversing the Mg/Li ratio of 40 to achieve a Li/Mg ratio of 4.6. This work reports the manufacturing strategy of hybrid membranes based on porous frameworks and 2D materials for precise ion separation.

Nanocellulose demonstrates remarkable application potential in the pharmaceutical field due to its unique physicochemical properties. However, the rapid and multidisciplinary development in this field urgently requires systematic analysis of technological topics to identify future research directions. Based on 1822 patents related to pharmaceutical nanocellulose (1982–2024) from the incoPat database, this study integrates topic evolution models and frontier identification algorithms to conduct a thematic analysis, supplemented by literature validation. The results indicate a clear evolutionary trend in technology, marked by a shift from basic material applications toward intelligent and precision systems. Meanwhile, the study identifies three major technological frontiers: hot technologies (e.g., composite dressings made of bacterial cellulose and chitosan that address pressing clinical needs), emerging technologies (e.g., 3D-printed aerogel bone scaffolds and gene therapy microcapsules representing innovative directions), and declining technologies (e.g., certain light-responsive drug carriers and multifunctional composites limited by inherent drawbacks). Literature validation further consolidates these findings, underscoring nanocellulose as an ideal candidate for pharmaceutical R D due to its excellent biocompatibility and customizability; nevertheless, its clinical translation still commonly faces core challenges, including manufacturing processes, targeted delivery efficiency, and immunogenicity control. Based on this, the study outlines a future direction with the central goal of bridging the “innovation-translation gap” and promoting a substantive leap from functional composite development toward precise intervention in life processes. Achieving this transition relies on two pillars: first, overcoming translational bottlenecks in standardization, safety, and targeted delivery at the application level; and second, enabling intelligent material design and integration of interdisciplinary approaches at the technological level. The findings from this study offer a strategic framework essential for guiding future research and accelerating the clinical translation of nanocellulose in the pharmaceutical field.

Limited immune cell infiltration is the main reason for poor immunotherapeutic efficacy in colorectal cancer patients. Here we design a peptide-based nanorobot that recognizes PD-L1 and breaks cancer cell membranes by in situ forming fibrils through a pH-responsive module. The nanorobot shows long retention in targeted tumours (>120 h) through interaction with PD-L1 and blocks PD-1/PD-L1 to activate the T cell killing effect. At the same time, in the tumour microenvironment (pH 6.5), it forms fibrils that break the cancer cell membrane, inducing immunogenic cell death with the release of damage-associated molecular patterns and the subsequent infiltration of T cells. The nanorobot shows higher therapeutic efficacy than the regimen of αPD-L1+oxaliplatin in a variety of colorectal-cancer-tumour-bearing mouse models and has good biocompatibility due to the targeted breakage of cancer cells, exhibiting great potential for colorectal cancer immunotherapy in clinic.

Chemo-gene combination therapy offers a promising strategy to overcome the challenges of the tumor microenvironment, aiming to enhance therapeutic efficacy and reduce side effects. However, the distinct properties of nucleic acids and chemotherapeutic agents present significant challenges for their co-delivery using nanoparticles (NPs). This study proposes a novel nanoparticle delivery system based on π–π stacking interactions to facilitate the co-delivery of siRNA and irinotecan hydrochloride (IR). A series of amphiphilic block copolymers with various aromatic side groups were synthesized via living ring-opening polymerization (ROP). Complexes of siRNA and IR were initially formed through electrostatic interactions. Subsequently, polymer/nucleic acid/chemotherapeutic composite NPs were assembled via π–π stacking interactions between the aromatic groups on the polymers and those on the IR molecules. Particle size (Dh) and zeta potential (ζ) of NPs were measured by DLS. IR loading efficiency (EE) and loading capacity (LC) were determined by UV–Vis. HeLa-Luc cells were treated with polymer@siPLK1 IR NPs to assess luciferase gene silencing and cytotoxicity via the MTT assay. Block copolymers with fine-tuned chemical structures and narrow molecular weight distributions were obtained via ROP of benzyl- or naphthyl-substituted valerolactone monomers using mPEG as the initiator. Selected polymers (PPLB6, PPLN5, PPLN6, and PPLV4) can bind siRNA IR complexes via π–π stacking interactions and form spherical NPs (Dh = 121–173 nm; ζ = − 11.8 to − 22.4 mV). Aromatic group-containing polymers achieved higher IR EE (57.5–63.9

Enhancing cancer immunotherapy using methods that induce immunogenic cell death (ICD) can significantly improve its effectiveness and profoundly influence its role as a highly efficient cancer treatment strategy. However, the limited penetration of cytotoxic T cells into tumors, owing to dense tumor fibrosis, remains a significant barrier to immunotherapy. A tumor microenvironment-sensitive intelligent dual-drug delivery system was developed to simultaneously deliver epigallocatechin-3-gallate (EGCG) and doxorubicin (DOX) to mitochondria. EGCG enhanced the mitochondria-targeted action of DOX and increased damage to the mitochondrial electron transport chain which facilitated capturing electrons in the mitochondrial matrix of DOX. Subsequently, DOX molecules form a semiquinone intermediate and electrons are transferred to oxygen to generate reactive oxygen species (ROS) that induce mitochondrial apoptosis. These results indicate that EGCG amplifies the combined effects of chemo/chemodynamic therapy of DOX, demonstrating a pronounced synergistic ICD effect that recruits CD8+ T cells to the tumor microenvironment (TME). In addition, EGCG promotes T-cell infiltration into tumor tissues by inhibiting the transforming growth factor-β signaling pathway, thereby significantly enhancing antitumor efficacy. This study advances the efficacy of immunotherapy through bidirectional synergy, which not only enhances intrinsic tumor immunogenicity but also overcomes the extrinsic physical barriers of tumors, providing a new direction for the development of broadly applicable immunotherapies.

Synthetic dyes, such as malachite green (MG), are widely used in the textile industry but pose significant environmental risks due to their toxicity. In this study, a highly efficient salt-tolerant bacterial strain, Vibrio natriegens SWS5, was isolated and identified through morphological, physiological, biochemical, and 16S rRNA gene sequence analyses. Systematic investigations were conducted to optimize degradation conditions, analyze enzyme activities, elucidate degradation pathways, and assess detoxification effects. The optimal degradation conditions were determined as follows: peptone 7.5 g/L, NaCl 20 g/L, Fe2+ 0.04 g/L, pH 7, temperature 30 degrees C, and shaking speed 220 rpm. Under these conditions, SWS5 achieved 97.88 % degradation of MG (100 mg/L) within 168 hours. After MG added, enzyme activity assays revealed in dye-decolorizing peroxidase (823 U/L), laccase (358 U/L), and manganese peroxidase (0.204 U/L) activities. HPLC-MS analysis identified key intermediates, enabling the proposal of two potential MG degradation pathways. Toxicity assessments using microbial tests and zebrafish models demonstrated a significant reduction in the toxicity of degradation products. Transcriptome sequencing provided novel insights into the regulatory pathways of MG degradation, offering a theoretical foundation for the bioremediation of MG contaminated wastewater. Vibrio natriegens was demonstrated for the first time to degrade triphenylmethane dyes, especially MG, in high-salinity environments. This study highlights the potential of Vibrio natriegens SWS5 as an efficient and eco-friendly solution for dye wastewater treatment.

Efficient intracellular protein delivery is of great importance for the development of protein-based therapy and modern biotechnologies. However, the hydrophilic and macromolecular nature of proteins greatly hinders their ability to cross cell membranes. Herein, a calixarene modification strategy for the intracellular delivery of protein drugs is developed. The decoration of sulfonate azocalix[4]arene (SAC4A) on proteins results in a nano-multivalent effect between Protein-S and amino acids on the cell surface, leading to efficient intracellular delivery of the protein via the clathrin-mediated endocytic pathway. By using SAC4A as a novel ligand, this calixarene modification strategy efficiently delivers 7 proteins, bovine serum albumin (BSA), trypsin (TRY), horseradish peroxidase (HRP), α-chymotrypsin (α-Chyt), lysozyme (LYZ), cytochrome C (Cyt C) and ribonuclease A (RNase A), into cells and significantly enhances the cytotoxicity of Cyt C and RNase A. Moreover, SAC4A-modified Cyt C demonstrates markedly enhanced antitumor efficacy in 4T1-bearing mice without notable side effects. Considering that these proteins are varied in molecular weight and isoelectric point, this calixarene modification strategy provides a platform technology for intracellular protein delivery and the development of protein drugs targeting intracellular pathways.

Erlotinib (ERL) is a first-line targeted therapy for patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). However, its effectiveness is hindered by acquired resistance and poor bioavailability. Carrier-free nanodrugs are a research hotspot due to their efficient targeting, high drug loading capacity, and the absence of any excipients. Herein, we report an advanced self-delivery system for multimodal NSCLC therapy using a computer-aided strategy. First, we developed a novel heterodimer, ERL-SSQM (ERL conjugated with QM-OH-a hydrophobic aggregation-induced emission fluorophore-via a disulfide bond [SS]), which serves as both cargo and carrier material. Self-assembly is driven by multiple noncovalent interactions, including it-it stacking and sulfur bonds. Subsequently, an ERL-SS-QM-based "triadic" drug delivery nanoplatform comprising 21 variants was developed. A case study on ursolic acid (UA)-loaded ERL-SS-QM nanoparticles (named UA@ERL-SS-QM NPs) revealed narrow size distribution, small particle size, and well stabilized (zeta potential =-28.9 mV). The UA@ERL-SS-QM NPs demonstrated concentration-dependent toxicity against targeted A549 cells (IC50 = 4.36 mu M), outperforming free monomeric drugs ERL (IC50 = 12.94 mu M) and UA (IC50 = 12.21 mu M), indicating good efficiency. Conversely, these NPs exhibited minimal cytotoxicity in non-targeted BEAS-2B cells, suggesting favorable biocompatibility. Upon endocytosis and interaction with overexpressed GSH in A549 cells, the disulfide-bond linker is cleaved to release three components: ERL, UA (which downregulates beta-catenin/TCF4/CT45A2 signaling pathways, inducing apoptosis in ERL-resistant L858R/T790M mutant cells-a key factor in acquired resistance to ERL treatment), and QM-OH. Hence, this work provides a universal model for multifunctional NSCLC therapy that effectively addresses ERL resistance while enhancing cytotoxicity and biocompatibility.

Traditional wound care methods are less effective for infectious and diabetic wounds, highlighting an urgent need for effective strategies. The study aimed to design a self-healing hydrogel with antibacterial, antioxidant, and photothermal capabilities to treat infectious and diabetic wounds. Silver nanoparticles (AgNPs) were loaded into mesoporous polydopamine (MPDA) nanoparticles to form Ag@MPDA nanoparticles. Ag@MPDA was incorporated into the cationic guar gum-chitosan-boric acid (CCB) hydrogel to obtain the PA-CCB hydrogel. PA-CCB hydrogel exhibited excellent self-healing and adhesive properties, adapting well to the dynamic wound environment. PA-CCB hydrogel combined with photothermal therapy (PTT) could effectively eradicated E. coli (99.9 %) and S. aureus (99.7 %). The PA-CCB hydrogel reduced excessive reactive oxygen species and promoted the migration of fibroblasts in vitro. In the infected mouse wound models, the PA-CCB hydrogel effectively inhibited bacteria. After combining with PTT, the antibacterial ability of the PA-CCB hydrogel was further enhanced. In the diabetic mouse wound models, the PA-CCB hydrogel reduced the inflammatory level of wound tissue. In both models, after combining with PTT, the PA-CCB hydrogel exhibited further improvements in angiogenesis, collagen deposition, and re-epithelialization. By integrating multifunctional hydrogel with PTT, the PA-CCB hydrogel exhibited broad application potential for infectious and diabetic wounds.

The efficacy of STING (stimulator of interferon genes) agonists is due to various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours, and a complex balance between tumour control and progression. Here we report a universal STING mimic (uniSTING) based on a polymeric architecture. UniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways. Intratumoural or systemic injection of uniSTING-mRNA via lipid nanoparticles (LNPs) results in potent antitumour efficacy across established and advanced metastatic tumour models, including triple-negative breast cancer, lung cancer, melanoma and orthotopic/metastatic liver malignancies. Furthermore, uniSTING displays an effective antitumour response superior to 2′3′-cGAMP and ADU-S100. By favouring IRF3/IFN-I activity over the proinflammatory NF-κB signalling pathway, uniSTING promotes dendritic cell maturation and antigen-specific CD8 + T-cell responses. Extracellular vesicles released from uniSTING-treated tumour cells further sensitize dendritic cells via exosome-containing miRNAs that reduced the immunosuppressive Wnt2b, and a combination of LNP-uniSTING-mRNA with α-Wnt2b antibodies synergistically inhibits tumour growth and prolongs animal survival. Collectively, these results demonstrate the LNP-mediated delivery of uniSTING-mRNA as a strategy to overcome the current STING therapeutic barriers, particularly for the treatment of multiple cancer types in which STING is downregulated or absent.

Topical eyedrop administration is identified as an ideal non‐invasive strategy for ocular drug delivery. However, multiple complex ocular barriers greatly restrict their effectiveness in the treatment of posterior ocular disease. Herein, a liposome‐based permeable eyedrops (pDrops) capable of overcoming multiple ocular barriers and achieving efficient posterior drug delivery is presented. pDrops have a core‐shell structure in which drugs are encapsulated inside the liposome core with a chitosan shell. This chitosan coating significantly enhances the pDrops’ binding to mucin in tears and facilitates the temporary opening of tight junctions in cornea/conjunctive epithelial cells, thereby achieving prolonged preocular retention and enhanced posterior segment drug delivery. In this study, hydrophilic ganciclovir (GCV) and hydrophobic curcumin (CUR) are employed as model drugs. Upon topical instillation, pDrops effectively overcome ocular barriers and delivered GCV to the posterior segment in both rat and rabbit eyes. Notably, CUR delivery by pDrops demonstrates significantly enhanced therapeutic efficacy in light‐damaged retina of mice. Considering that pDrops can deliver both hydrophobic and hydrophilic drugs to the posterior segment of the eye, it can potentially become a feasible platform for the non‐invasive delivery of various drug molecules and improve the treatment efficiency of posterior ocular diseases.

The local microenvironment where tumors develop can shape cancer progression and therapeutic outcome. Emerging evi-dence demonstrate that the efficacy of immune-checkpoint blockade (ICB) is undermined by fibrotic tumor microenviron-ment (TME). The majority of hepatocellular carcinoma (HCC) develops in liver fibrosis, in which the stromal and immune components may form a barricade against immunotherapy. Here, we report that nanodelivery of a programmed death-ligand 1 (PD-L1) trap gene exerts superior efficacy in treating fibrosis-associated HCC when compared with the conventional monoclonal antibody (mAb). In two fibrosis-associated HCC models induced by carbon tetrachloride and a high-fat, high -carbohydrate diet, the PD-L1 trap induced significantly larger tumor regression than mAb with no evidence of toxicity. Mech-anistic studies revealed that PD-L1 trap, but not mAb, consis-tently reduced the M2 macrophage proportion in the fibrotic liver microenvironment and promoted cytotoxic interferon gamma (IFNg)+tumor necrosis factor a (TNF-a)+CD8+T cell infiltration to the tumor. Moreover, PD-L1 trap treatment was associated with decreased tumor-infiltrating polymorpho-nuclear myeloid-derived suppressor cell (PMN-MDSC) accu-mulation, resulting in an inflamed TME with a high cytotoxic CD8+T cell/PMN-MDSC ratio conductive to anti-tumor im-mune response. Single-cell RNA sequencing analysis of two clinical cohorts demonstrated preferential PD-L1 expression in M2 macrophages in the fibrotic liver, thus supporting the translational potential of nano-PD-L1 trap for fibrotic HCC treatment.

Effective strategies for accurate differentiation of the vulnerable atherosclerosis (AS) plaques at molecular level for clinical diagnosis have yet been developed. Herein, a versatile SAmOCP nanoprobe, is constructed by sealing up the multinuclear gold self-assembled nanospheres by hollow mesoporous silicon shell and then decorating the surfaces with Chlorine e6 (Ce6)-conjugated osteopontin antibody (OPN Ab), followed by filling the internal cavity with perfluoropentane (PFP) for precise in vivo targeting and multi-modal imaging of the vulnerable AS plaques. SAmOCP nanoprobes actively recognize the foam cells and specifically target the vulnerable AS plaques in vivo. Relying on the exceptional photo-to-heat conversion properties resulting from enhanced localized surface plasmon resonance (LSPR) effects of Au self-assembled particles, the encapsulated liquid PFP could transform into abundant microbubbles when AS plaque-rich regions were overheated by 808-nm laser irradiation, enabling hyperthermia-enhanced microbubbles generation, thereby endowing nanoprobes with significantly enhanced ultrasonic imaging capacity. SAmOCP nanoprobes exhibit a triple-modality diagnostic efficacy of ultrasound/ fluorescence/photothermal imaging for in vivo precise detection of vulnerable AS plaques at molecular level. Together, SAmOCP nanoprobes overcome the difficulty in identifying the vulnerable AS plaque for clinic practice, holding great promise for vulnerable AS diagnosis.