Muscle-invasive bladder cancer (MIBC) is an aggressive urological malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) driven by dysregulated oncogenic metabolism. The oxidoreductase NAD(P)H:quinone oxidoreductase 1 (NQO1) stabilizes the core metabolic regulator hypoxia-inducible factor 1α (HIF-1α), which further transcriptionally activates the homeobox transcription factor SIX1, forming a coordinated NQO1/HIF-1α/SIX1 signaling axis that drives metabolic reprogramming and immune evasion in MIBC, yet targeted therapies disrupting this metabolic-immune nexus remain clinically unavailable. Here, we developed a biomimetic macrophage membrane-cloaked nanoplatform (MMP@siN/NC) for targeted co-delivery of NQO1-targeting siRNA (siNQO1) and the SIX1 small-molecule inhibitor NCGC, with a PEG-PDLLA/DOTAP hybrid core enabling prolonged systemic circulation, enhanced tumor targeting, efficient cellular internalization, facilitated endosomal escape, and synergistic drug release. In vitro, MMP@siN/NC exerted robust cytotoxicity against MIBC cells, induced potent immunogenic cell death (ICD), and suppressed aerobic glycolysis and tricarboxylic acid (TCA) cycle flux via axis blockade, which further promoted dendritic cell maturation, M1 macrophage polarization, and tumor-specific T-cell priming. In vivo, MMP@siN/NC potently inhibited tumor growth, elicited a systemic abscopal effect, and established durable anti-tumor immune memory in subcutaneous MIBC models, with strong synergistic efficacy in combination with anti-CTLA-4 (αCTLA4) immune checkpoint blockade. Critically, in a clinically relevant orthotopic MIBC model, the nanosystem exhibited excellent tumor accumulation, significant therapeutic efficacy, prolonged survival, and a favorable safety profile. Collectively, this work validated the NQO1/HIF-1α/SIX1 axis as a targetable metabolic-immune driver in MIBC, and presented a translatable nanotherapeutic strategy to simultaneously disrupt tumor metabolism and reactivate anti-tumor immunity for MIBC treatment.

In this study, we designed a lignin-based nanocarrier system with dual-stimuli responsiveness to the acidic pH and elevated glutathione (GSH) levels in the tumor microenvironment, and doxorubicin (DOX) was loaded to develop a nanomedicine delivery platform for antitumor treatment. Under the optimized conditions, uniform lignin-based nanoparticles with a diameter of approximately 150 nm and well-controlled physicochemical properties were successfully prepared. In vitro release studies confirmed the selective drug release under simulated tumor conditions (pH 6.5, 10 mM GSH). Biological evaluation revealed that the drug-loaded nanoparticles exhibited potent cytotoxicity against 4T1 breast cancer cells, while maintaining over 85% viability in normal cells, indicating good biocompatibility. In 4T1 tumor-bearing mice, the engineered nanocarriers demonstrated significantly enhanced therapeutic efficacy, achieving 71.84% tumor growth inhibition compared to that of 58.78% with free DOX, along with reduced systemic toxicity. In summary, this study demonstrates the successful transformation of sustainable lignin into an efficient therapeutic platform via precise chemical modification, effectively combining biopolymer advantages with stimulus-triggered drug release for more promising and biodegradable nanocarriers for cancer therapy.

Shape memory polymers (SMPs) with remote activation capabilities have garnered significant attention in biomedical applications. However, traditional activation methods exhibit limitations in tissue penetration depth and spatial-temporal control precision. Here, we report a multifunctional SMP system that synergistically integrates Fe3O4 nanoparticles and neodymium-iron-boron (NdFeB) microparticles to achieve simultaneous magnetic navigation and dual-mode thermal activation. The NdFeB microparticles, magnetized under external magnetic fields, provide superior magnetic moments for precise navigation control, while Fe3O4 nanoparticles enable both near-infrared II (NIR-II) photothermal conversion and magnetothermal heating under alternating magnetic fields (AMF). Additionally, the resulting magnetic polyurethane (MPU) exhibits excellent shape memory performance with rapid activation kinetics and high recovery ratios while maintaining superior mechanical properties and biocompatibility. Cell viability studies demonstrate minimal cytotoxicity, and animal experiments confirm successful magnetic navigation, precise shape recovery, and the absence of inflammatory responses in physiological environments. The findings demonstrate that this integrated MPU platform has significant potential for applications in minimally invasive surgical instruments, smart tissue scaffolds, and targeted therapeutic delivery systems.

Near-infrared (NIR) light-responsive shape memory polymers (SMPs) show great promise for biomedical applications, but conventional photothermal agents suffer from high cost, complex preparation, or poor biocompatibility, while lignin-based alternatives exhibit insufficient photothermal conversion efficiency. Herein, we developed a novel strategy to enhance photothermal performance of lignin through sequential demethylation modification and Fe3+ complexation for constructing NIR light responsive SMPs. Dealkaline lignin (DL) was first demethylated using iodocyclohexane to produce demethylated lignin (DDL) with increased catechol content, which was then incorporated into polycaprolactone-based polyurethane synthesis followed by Fe3+ complexation. Results showed that DDL-Fe3+ complexes have significantly enhanced photothermal conversion performance, and the resulting PU-DDL+Fe3+ polyurethane with 0.5 wt

Conventional chemotherapy and radiotherapy damage normal tissues due to off-target toxicity, impairing patient prognosis. Chemoradiotherapy (CRT)—the concurrent use of chemotherapy and radiotherapy—has gained considerable attention, as it suppresses primary tumors and reduces metastasis. However, dose-limiting drug toxicity remains a major barrier to clinical CRT. To mitigate adverse effects and improve drug bioavailability, nano-sensitizer (NS)-mediated CRT has become a research focus. Nonetheless, unique tumor microenvironmental features, including hypoxia, abnormal vasculature, elevated reactive oxygen species, mild acidity, dense extracellular matrix, and immunosuppression, severely compromise NS efficacy. Accordingly, smart NS designed to surmount these microenvironmental barriers represent a key direction in drug development. This review summarizes recent advances in tumor microenvironment-targeted NS and their preclinical and clinical applications, aiming to deepen understanding of microenvironmental challenges in CRT and facilitate the development of potent NS.

To explore the aggregation behavior of small molecules and macromolecules at different scales, this study employed aggregation-induced emission (AIE) molecule tetraphenylethylene-polyol (TPE-4OH) as a polyol initiator to synthesize four-armed poly(l-lactic acid) (4a-TPE-PLLA) with varied chain lengths. Moreover, comparative studies with pentaerythritol-initiated four-armed PLLA revealed significant mutual regulatory relationships between self-aggregation of TPE groups and PLLA crystallization. Lower glass transition temperatures (48.0°C of 4a-TPE-PLLA-S and 49.4°C of 4a-TPE-PLLA-M) and rheological results indicated that when PLLA chains are short (28 repeating units) or medium (48 repeating units) in length, TPE groups weakened the PLLA interchain interactions and promoted the segmental mobility of of PLLA chains. While longer PLLA chains (78 repeating units) were easier to restrict the conformation of TPE, which showed higher photoluminescence quantum yield (PLQY) values. In-situ polarized microscopy revealed TPE aggregates promoted the nucleation of PLLA. Higher PLQY was observed after 4a-TPE-PLLA crystallization, especially, the PLQY of 4a-TPE-PLLA-M increased from 58.23% to 65.36%. And 4a-TPE-PLLA also showed the potential application of phase separation indicator due to its fluorescence properties. This work provides some insights into the multi-scale aggregation mechanisms of PLLA chains and AIE molecules.

The use of physical barriers is an effective strategy for preventing postoperative adhesion, a prevalent complication in clinical abdominal surgeries. However, the current anti-adhesion barriers face limitations in precisely regulating key cellular responses during tissue repair. In this study, a multi-modal synergistic degradable antiadhesion membrane was developed via coaxial electrospinning of poly(4-hydroxybutyrate) (P4HB), polyglycolic acid (PGA), and diclofenac sodium (DS). The designed membrane features a densely packed fibrous architecture, exhibiting over 97 % inhibition efficiency against fibroblasts interlayer penetration in vitro. The rapid initial release of DS synergizes with PGA-mediated biological functions to suppress fibroblast-tomyofibroblast differentiation, and to significantly mitigate early-stage pathological changes. This cascade effect ultimately leads to reduced collagen deposition and significantly diminished adhesion formation, as demonstrated in a mouse cecal and peritoneal abrasion model. Furthermore, the membrane demonstrates exceptional flexibility and enhanced hydrophilicity, ensuring conformal coverage of complex three-dimensional wounds. The integration of structural design, controlled drug release, and dynamic biological modulation renders this multifunctional barrier as a promising candidate for next-generation clinical anti-adhesion applications.

Type 2 diabetes mellitus (T2DM) has evolved into a global health crisis, driving a silent yet progressive hepatic pathological cascade that advances from nonalcoholic fatty liver disease to fibrosis and ultimately to cholangiocarcinoma with a high probability. However, the covert nature and gradual progression of this pathological cascade pose significant challenges for early detection and continuous monitoring. Herein, we design a multiparameter magnetic resonance imaging (MRI) strategy for visually monitoring T2DM-associated hepatic dysfunction across disease stages in vivo, based on dual-modality NaGdF4 nanoprobes. Owing to the long tumbling time (τR), NaGdF4 nanoprobes can enhance longitudinal relaxivity (r1) to brighten T1-weighted signals, while the regular arrangement of Gd3+ in the crystal induces magnetic anisotropy, creating local static magnetic field heterogeneity that generates negative signals in susceptibility-weighted imaging (SWI) sequences. The multiparametric MRI strategy combined with pathological analysis comprehensively characterized hepatic disease progression in a T2DM mouse model and confirmed the association between T2DM-induced liver injury and precancerous biliary transformation. With the NaGdF4 nanoprobes, key imaging features were successfully identified, including impaired hepatic metabolic capacity with prolonged contrast retention, hypoxia-induced neovascularization, and biliary tract lesions progressing from intermediate reactive hyperplasia to advanced cholangiocarcinoma. This multiparameter MRI approach provides noninvasive, high-resolution insights into hepatic metabolic dysfunction, vascular remodeling, and biliary pathology, offering a powerful tool for early diagnosis and prognostic assessment of T2DM-associated liver complications.

Brain metastases (BrM) represent a frequent and devastating complication of advanced solid tumors, characterized by poor prognosis and limited therapeutic options due to the restrictive blood-brain barrier and an immunosuppressive tumor microenvironment (TME). Although the stimulator of interferon genes (STING) pathway is a promising immunotherapeutic target, its clinical application has been hampered by systemic toxicity, inadequate tumor selectivity, and insufficient delivery to intracranial sites. To overcome these challenges, we developed a composite nanosystem, (PC-A)/M nanoparticles, for the targeted codelivery of the STING agonist diABZI and paclitaxel (PTX). This system employs a dual-responsive mechanism based on pH and glutathione (GSH), where the nanoparticle structure first dissociates in the acidic TME to facilitate cellular uptake and subsequently releases its therapeutic cargo in response to the elevated intracellular GSH levels of cancer cells. PTX induces immunogenic cell death and direct apoptosis, while the STING agonist disrupts neovasculature and activates innate immunity to reprogram the local immune environment. This synergistic combination promotes dendritic cell maturation, M1 macrophage polarization, and cytotoxic T-cell recruitment. Our strategy aims to concurrently target primary tumors and BrM, establishing a durable antitumor immune response, and establishes a promising therapeutic strategy for solid tumor BrM.

Poor repair outcomes of abdominal wall soft tissue defects often lead to hernia recurrence and tissue adhesion, thereby increasing the medical burden. An ideal repair material should simultaneously fulfill the requirements of anti-adhesion properties, wet tissue adhesion capability, biodegradability, and the ability to promote functional tissue regeneration. Herein, inspired by the natural abdominal wall architecture, we designed a biomimetic Janus-structured repair patch, denoted as PS-PDH. This patch integrates a biodegradable poly(4-hydroxybutyrate) (P4HB) electrospun fibrous membrane with a glutathione-responsive degradable poly(sulfobetaine methacrylate) (PSBMA) hydrogel via polydopamine (PDA). It exhibits excellent asymmetric adhesive properties: the fibrous side facilitates cell adhesion and proliferation, while the hydrogel side effectively resists cell and protein adhesion. Furthermore, PS-PDH possesses robust mechanical properties, enabling it to adapt to dynamic tissue deformation. Notably, the patch effectively scavenges free radicals and intracellular reactive oxygen species (ROS), while promoting macrophage polarization from the pro-inflammatory M1 to the pro-regenerative M2 phenotype. In a mouse full-thickness abdominal wall defect model, PS-PDH effectively prevented postoperative adhesion and fibrosis, modulated the inflammatory microenvironment, and promoted functional muscle and vascular regeneration. Therefore, this biomimetic Janus-structured patch offers a reliable and highly clinically translatable strategy for the functional repair of abdominal wall soft tissue defects.

Glioblastoma (GBM) is recognized as one of the most aggressive and devastating primary brain cancers, posing a significant clinical challenge. The blood-brain barrier (BBB) significantly impedes therapeutic drug delivery, contributing to treatment resistance and poor prognosis with GBM. As a choline analogue, 2-methylacryloxyethyl phosphocholine (MPC) has been identified to cross the BBB by binding to nicotinic acetylcholine receptors (nAChRs) and choline transporters (ChTs) on the surface of the brain endothelial cells. In this study, aiming at utilizing this unique property to realize targeted drug delivery to brain tumors, a novel poly(2-methylacryloxyethyl phosphocholine) (pMPC-CHO)-based pH-responsive nanoparticles (NPs) drug delivery system (DDS) was developed via a simple strategy. By copolymerizing MPC monomer and oligo-poly(ethylene glycol) monomer containing aldehyde group to form a hydrophilic shell and synthesizing amphiphilic chitosan polymer-paclitaxel conjugate as the core, pH-responsive nano DDS (PC/M NPs) were obtained. pMPC-CHO enhances biocompatibility and BBB crossing ability. In the tumor microenvironment, PC/M NPs release positively charged chitosan NPs due to the broken imine bond, promoting cancer cell uptake and transcytosis, and then intracellular glutathione (GSH) activates paclitaxel to kill tumor cells. This pH and GSH-dual-responsive nano DDS integrates BBB crossover and tumor penetration, presenting an innovative and promising drug delivery platform for GBM treatment, which can balance prolonged circulation time, efficient BBB crossover, and enhanced tumor infiltration.

Conventional medical polyurethanes often suffer from slow physiological degradation, and efforts to accelerate degradation typically compromise their essential material properties. In this work, polycaprolactone-based polyurethanes were synthesized using oligo(glycolic acid) (oligoGA) and 1,4-butanediol (BDO) as chain extenders. The chemical and physical structures of polyurethanes were characterized by 1H NMR, FTIR, SAXS and AFM. By systematically adjusting the proportion of oligoGA, the tensile toughness of polyurethane with oligoGA as chain extender (PUGA) was 205 % higher than that of polyurethane using BDO (PU). This significant enhancement is primarily attributed to the regulation of microphase separation and H-bonding networks by oligoGA. Furthermore, increasing the proportion of oligoGA led to a gradual increase in the enzymatic degradation rate of polyurethanes, accompanied by a change in the degradation mechanism. PUGA also exhibited excellent biocompatibility and a body temperature-responsive shape memory effect, making it a promising candidate for biomedical applications. The incorporation of biodegradable oligoGA chain extender provides an effective strategy for fine-tuning the mechanical properties and degradability of polyurethanes, making them adaptable to diverse medical scenarios.

Catheter-related thrombosis (CRT) and catheter-related bloodstream infections (CRBSI) are serious complications that affect the therapeutic effect in the course of treatment using peripherally inserted central venous catheters. In this paper, a composite multifunctional antifouling coating with hybrid super-hydrophilic and super-hydrophobic structure is constructed by atomic transfer radical polymerization between zwitterionic 2-methacryloyloxy ethyl phosphorylcholine and 4,4,4-trifluorocrotonic acid and firmly immobilized onto the catheters by covalent grafting. The composite coating exhibits a micro-phase separated structure and endows the modified catheters with better antibacterial and antithrombotic properties than solely super-hydrophilic or super-hydrophobic coating, by significantly reducing the adhesion of proteins (50 %), platelets and bacteria (95 % for E. coli and 87.5 % for S. aureus), and greatly decreasing the thrombosis (> 80 %) on the catheter in vitro. In in vivo rabbit and pig models, by ultrasonography, the thrombosis inside the veins of experimental animals receiving modified catheter is improved greatly. Besides, the coating shows good durability and biosafety, exhibiting great potential to meet the growing clinical demand for antifouling catheters in coping with CRT and CRBSI.

Chronic wounds are common complications for diabetic patients, characterized by difficult healing because of the persistent and excessive inflammatory response, susceptibility to infection, and a lack of effective contraction stress at the diabetic wound site. In this study, we develop a heterogeneous hydrogel patch through the in situ free radical polymerization of acrylamide (AM) in the presence of modified alginate (Alg-Cat) within a porous polyurethane foam (DDLPU-foam). The polyurethane foam containing demethylated dealkaline lignin-Fe3+ complex structures (DDL-Fe3+) with photothermal properties endows the patches with excellent near-infrared (NIR) light-responsive shape memory performance, allowing the pre-stretched patches to provide biaxial contraction for diabetic wounds under NIR light, while also providing broad-spectrum photothermal antibacterial properties. The Alg-Cat in the hydrogel phase contains disulfide-linked catechol, offering antioxidant activity and flexible tissue adhesion. In vivo tests demonstrate that the DDLPU/Alg-Cat patch effectively reduces the inflammation level of chronic wound and promote tissue reconstruction, accelerating wound healing through combined mechanical modulation function and antioxidant activity. This heterogeneous hydrogel patch possesses both mechanical modulation function and bioactivity, providing a novel and effective strategy for treating chronic diabetic wounds.

Poly(glycolic acid) (PGA), as a biocompatible polyester, is promising for packaging applications due to its excellent gas barrier properties. However, its mechanical brittleness limits its practical use. The blending modification of PGA with polyamide 6 (PA6) was investigated in this study, and the phase structure, rheological properties, thermal behavior, mechanical properties, barrier, and degradation properties of both binary and ternary blends were comprehensively evaluated. The results show that the incorporation of PA6 significantly enhanced the toughness of PGA while maintaining or even improving its tensile strength, overcoming the limitations of conventional PGA toughening methods. The introduction of a chain extender further enhanced the compatibility between PGA and PA6 phases, leading to further improved mechanical properties. Rheological analysis reveals an increased storage modulus and improved processability. Furthermore, the blends exhibit superior oxygen barrier properties compared with neat PGA and neat PA6, attributed to hydrogen bonding at the interface. These findings provide insights into designing hierarchically structured polymer blends for advanced packaging materials combining gas barrier efficacy, mechanical durability, and sustainable processability.

Shape memory polymers (SMPs) show promise in tissue engineering through programmable deformations, but developing SMPs with simultaneous excellent mechanical performance, shape memory capabilities, and bioactivity remains challenging. We synthesized novel polycaprolactone (PCL)-based shape memory polyurethanes functionalized with α-polyglutamic acid (α-PLGA) side chains (PU-PLGA). These materials exhibited crystallization temperatures of 1.4-2.4 °C and melting temperatures of 40-40.4 °C. The PU-PLGAs demonstrated excellent mechanical properties, with the 2% α-PLGA variant achieving 19.5 MPa tensile strength and 894.9% elongation at break. All PU-PLGAs displayed outstanding shape memory capabilities for complex shape programming. In vitro experiments showed good cell compatibility (>80% viability), with α-PLGA incorporation significantly enhancing rat bone marrow mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation. Conceptual implantation experiments demonstrated PU-PLGA's potential for tissue engineering scaffolds in bone defect repair applications.

Unlike conventional antibiotic antibacterial methods, photothermal antibacterial methods have fewer toxic side effects and do not result in drug resistance. However, because of the complex bacterial microenvironments, simple photothermal treatment cannot provide a good antibacterial effect. Thus, a dual-mode nanoantibacterial photothermal agent (MxNy) was constructed, which was composed of MXene QDs with excellent photothermal conversion effects and Nanoengineered Peptide-Grafted Hyperbranched Polymers (NPGHPs) with broad-spectrum antibacterial activity. MXene QDs in the assembly could be used to adjust the Zeta potential of the system so that the assembly system could change the type of dominant antibacterial activity, achieve broad-spectrum antibacterial characteristics, and form an antibacterial matrix. More surprisingly, with the increase in temperature, the antibacterial activity of antimicrobial peptides also increased. The photothermal conversion efficiency of the assembly reached 39.6%. In vitro and in vivo antibacterial experiments showed that the MxNy could significantly inhibit the proliferation of Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis after MXene QDs regulated the Zeta potential of the system, and the toxicity was negligible. Mouse experiments also proved that the wound recovered faster after MxNy near-infrared treatment. Therefore, the MxNy is a multifunctional collaborative antibacterial platform with good biological application prospects.

In shape memory polymers (SMPs) composed of semicrystalline polymers, their crystallization-melting process and the overall entropic elasticity of the material determine their shape memory behavior. In this work, cross-linked polyurethanes with polycaprolactone (PCL), poly(l-lactic acid) (PLLA), and poly(d-lactic acid) (PDLA) segments were designed, in which four-armed PCL served as the chemical cross-linking and polylactic acid (PLA) crystals acted as physical cross-linking. By adjusting the molecular weight of the four-armed PCL and the type of PLA crystals [homocrystals (HC) and stereocomplex (SC) crystals], the overall cross-linking degree of the material was controlled, and the crystallization behavior, mechanical properties, and shape memory behavior of the material were studied. The results indicated that both physical and chemical cross-linking significantly affect the mechanical properties and shape memory properties of materials. Moreover, polyurethane-contained SC exhibited a higher shape recovery ratio (Rr) and fixation ratio (Rf) than polyurethane-contained HC because SC provided higher entropy elasticity and promoted PCL crystallization. This study provides a method for synergistically enhancing Rf and Rr of SMPs, offering insights into the design of related materials.

Bladder cancer remains a significant clinical challenge, necessitating the development of innovative therapeutic strategies. Recent advancements have highlighted the potential of reactive oxygen species (ROS)-responsive drug delivery systems in cancer therapy. In this study, we introduce a novel treatment approach utilizing a ROS-responsive camptothecin (CPT) prodrug encapsulated within a chitosan nanocarrier, named CACPT. Cinnamaldehyde (CA), acting as a ROS generator, forms thioketal bonds with CPT to create a prodrug that responds selectively to the elevated ROS levels within the tumor microenvironment. Upon exposure to high ROS conditions, these thioketal bonds are cleaved, resulting in the simultaneous release of CPT and CA. The liberated CA further enhances ROS production, establishing a positive feedback loop that amplifies the therapeutic effect. The use of amphiphilic chitosan nanocarriers enhances the retention and penetration of the prodrug within bladder tissue, optimizing its therapeutic potential. Our experimental findings demonstrate that this self-enhanced ROS-responsive release promotes increased cellular uptake and significantly enhances the anticancer efficacy of CACPT. These results position CACPT as a promising candidate for intravesical therapy in bladder cancer, potentially overcoming current limitations in treatment options. The innovative combination of ROS-responsive mechanisms and chitosan nanocarriers represents a paradigm shift in bladder cancer therapeutics, offering a multifaceted approach with substantial promise for clinical translation.

Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593-5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.