Cancer immunotherapy has revolutionized the landscape of cancer treatment, particularly through the development of immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis. However, the therapeutic efficacy of these interventions is frequently hindered by the immunosuppressive tumor microenvironment (TME), which is characterized by hypoxia, poor immune cell infiltration, and impaired antigen presentation. To overcome these barriers, MP-GCZ has been developed as a self-oxygenating biomimetic nanomotor to synergistically reprogram the TME and enhance antitumor immune responses through integrated multimodal mechanisms. This nanosystem combines photothermal therapy (PTT), cuproptosis-induced immunogenic cell death (ICD), and localized immune checkpoint modulation to address the complex immunosuppressive network of the TME. By leveraging a metal-organic framework scaffold, MP-GCZ enables controlled delivery of therapeutic components that alleviate hypoxia, trigger immunogenic tumor cell death, and enhance adaptive immune responses. When activated by near-infrared irradiation, MP-GCZ enhances dendritic cell maturation, increases infiltration of cytotoxic T lymphocytes, thereby transforming immunologically "cold" tumors into inflamed, immunogenic environments. Preclinical studies demonstrate that this strategy effectively suppresses both primary tumor growth and distant metastases, driven by systemic antitumor immunity. MP-GCZ represents a promising comprehensive approach to overcoming TME-mediated resistance and may offer a valuable solution to enhance the clinical efficacy of cancer immunotherapy.

Shikonin (SHK) possesses potent antitumor activity; however, its severe non‑selective toxicity greatly limits the feasibility of conventional systemic administration for cancer therapy. Likewise, mild photothermal therapy (PTT) has intrinsic limitations, including inadequate induction of immunogenic cell death (ICD) and compensatory activation of immunosuppressive pathways, such as increased IDO1 activity and PD‑L1 expression. In the present study, low‑dose SHK and gold nanorods were co‑encapsulated within a supramolecular hydrogel (mPECT) and administered by intratumoral injection to achieve localized combination therapy with mild PTT. Mild PTT rapidly triggered antitumor immune activation within the immunosuppressive tumor microenvironment, whereas SHK sustained this response by suppressing PTT‑induced IDO1 activation and PD‑L1 upregulation and by markedly enhancing ICD. The mPECT hydrogel enabled prolonged local retention and controlled release of SHK, minimizing rapid systemic exposure while preserving therapeutic efficacy at the tumor site. This localized combination of SHK and mild PTT elicited a robust adaptive antitumor immune response that not only inhibited primary tumor growth but also suppressed the progression of untreated distant tumors and generated durable antitumor immune memory. These findings indicate that a single intratumoral administration of low‑dose SHK‑loaded hydrogel combined with mild PTT can induce potent systemic antitumor immunity, supporting the further development of localized SHK‑based therapeutic strategies for the treatment of immune‑cold tumors.

Vulvovaginal candidiasis (VVC) is a common fungal infection that significantly affects women's health worldwide. Antifungal agent therapies are not particularly effective for VVC and can further promote an imbalance in the vaginal microbiota, increasing recurrence. Nanozymes are currently being evaluated as an alternative therapy owing to their broad-spectrum antibacterial activity and negligible biological toxicity. However, their inherently low catalytic activity limits their antibacterial properties. In this study, an Mn,Fe-doped polyoxometalate (Mn,Fe-POM) nanozyme was successfully constructed as a potential treatment for VVC through the synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT). The developed approach was based on Lactobacillus in the vagina, which provides a suitable microenvironment for promoting the peroxidase (POD)-like activity of Mn,Fe-POM. Mn,Fe-POM-bound Lactobacillus exhibited excellent near-infrared-triggered POD-like activity for CDT and noteworthy photothermal performance for PTT. Electron transfer between Fe2+/Fe3+ and Mn3+/Mn4+ provided abundant active sites, increasing POD-like catalytic activity based on Fenton-like mechanisms and amplifying the CDT potential. In vitro, Mn,Fe-POM demonstrated a remarkable synergistic effect in killing Candida albicans (C. albicans) and disrupting the biofilm, while also preserving the Lactobacillus species. This outstanding anti-C. albicans activity was achieved without significant damage to the vaginal mucosa cells, reducing vaginal inflammation in an in vivo VVC mouse model. The increased Lactobacillus proportions and reduced C. albicans numbers allowed the reconstruction of healthy vaginal microbiota to decrease infection recurrence. This study presents an innovative and promising therapeutic approach for VVC.

Bioadhesives in surgery are receiving increasing attention because of their ease of handling and desirable ability to promote wound closure; however, their mechanical mismatch with skin tissue and insufficient multifunctionality hinder clinical application. A mechanically compliant, multifunctional bioadhesive hydrogel (PATF) composed of polyacrylamide (PAM), alginate (Alg), tannic acid (TA), and ferric chloride (FeCl3) has been developed for rapid wound repair. The covalently crosslinked PAM network provides structural integrity, while multiple noncovalent interactions (Alg/Fe[3+] ionic bonds, hydrogen bonds, and TA/Fe[3+] coordination) endows the hydrogel with skin-like modulus (∼25 kPa), improved toughness (328.9 kJ/m[3]), ultra-stretchability (∼2500% strain), and low hysteresis (<21%). PATF hydrogel exhibits outstanding conformational adhesion with the skin surface, 5.25-fold stronger than that of commercial 3M Tegaderm, and can be readily detached on demand in the presence of FeCl3 solution. Furthermore, multifunction involving antioxidant capacity, photothermal therapy-mediated antibacterial efficacy, comparable conductivity to native skin tissues, and superior hemostatic performance enables PATF hydrogel (with near-infrared irradiation) to suppress inflammation, promote collagen deposition, and enhance angiogenesis, collectively accelerating healing of infected full-thickness skin wounds within 7 days. These integrated mechanically and biologically compliant properties make PATF hydrogel a versatile candidate for fast, effective wound repair. STATEMENT OF SIGNIFICANCE: This study develops a rationally designed mechanically compliant multifunctional bioadhesive hydrogel (PATF) through a hybrid crosslinking network. The covalently crosslinked PAM network ensures structural integrity, while multiple non-covalent interactions endow the PATF hydrogel with skin-like modulus, improved toughness, ultra-stretchability, and low hysteresis. It exhibits outstanding conformational adhesion with skin surface, which is 5.25-fold stronger than that of 3M Tegaderm, and could be detached easily on demand. Its antioxidant capacity, PTT mediated antibacterial efficacy, comparable conductivity to native skin tissues, and superior hemostatic performance enable PATF hydrogel to suppress inflammation, promote collagen deposition, and enhance angiogenesis, collectively accelerate infected full-thickness skin wound healing within 7 days and hair follicle regeneration, making it a promising candidate for wound management.

This study is aimed at examining the computational modeling of the blood flow of a trihybrid nanofluid with nanoparticles such as Ag, Au, and Cu to simulate the hemodynamics parameters and heat transfer within a constricted channel geometry that directly parallels the flow conditions in a stenosed artery. The flow is defined as an unsteady, incompressible, laminar Newtonian fluid, with blood exhibiting Newtonian properties at elevated shear rates. An algorithm for mass, velocity, and energy, as well as a fine element-sized mesh, was developed using the computational fluid dynamics (CFD) technique based on the finite element method. Here, systematic observation of the effect of varying nanoparticle volume fractions (ϕ = 3%, 9%, 15%) and Reynolds numbers (Re) on the resulting flow velocity profiles. Although maximal velocity is geometrically concentrated at the stenosis throat, the critical determining factor of patient danger is the concentration-dependent change in fluid viscosity. Increasing ϕ raises effective viscosity (Brinkman model), progressively flattening the velocity profile into a blunt, plug-like regime; paradoxically, this near-uniform plug, lacking the gradual wall-to-core velocity gradient of a parabolic profile, is unable to resist the adverse pressure gradient at the abrupt poststenotic expansion, causing simultaneous cross-sectional deceleration and abrupt flow separation that sustains larger, more energetic recirculation zones than those observed at lower ϕ. This disturbed distal flow that generates large and persistent recirculation zones downstream of the stenosis, which are associated with increased thrombotic risk due to disturbed flow patterns. Conversely, the increase in ϕ drastically increases thermal conductivity, making the heat transfer process nearly independent of flow speed, that a key insight for forthcoming contained thermal therapies. Eventually, this research delivers a mechanistic link between fluid rheology, flow instability, and thrombotic risk, signifying that therapeutic strategies need to prioritize the management of fluid viscosity to stabilize poststenotic flow fields and mitigate associated cardiovascular complications. This work is the first effort to evaluate the impact of trihybrid nanofluid rheology on the exacerbation of poststenotic flow instability at clinically relevant Re. This reveals that a critical higher nanoparticle loading (ϕ) improves thermal conductivity. The present findings have direct significance for biomedical applications like targeted photothermal therapy (PTT), antimicrobial vascular intervention, and nanoparticle-mediated drug delivery in cardiovascular disease management. The computed 18% enhancement in conductive heat flux at ϕT = 15% further establishes a quantitative performance baseline for the design of nanofluid-based thermal management systems in biomedical microdevices.

An innovative dual-wavelength-responsive GMMC-Pdots-Ag hydrogel was fabricated for the treatment of polymicrobial-infected liver and skin defects. The hydrogel is based on a dynamic double-network architecture composed of gelatin methacryloyl (GelMA), O-carboxymethyl chitosan (O-CMC), and 4-arm poly(ethylene glycol) benzaldehyde (4-arm-PEG-DF), co-loaded with PtOEP-doped T2-DPPT@NH2 polymer dots (Pdots) and L-histidine-stabilized silver nanoparticles (His-Ag NPs). Upon exposure to near-infrared (NIR) radiation at 808 nm, the Pdots induce a localized photothermal effect (PTT). Combined with the weakly alkaline microenvironment and temperature increase, this effect triggers the controlled release of Ag[+]. This dual response enables rapid antibacterial activity and biofilm eradication during the acute stage of inflammation. During the subsequent repair phase, 380 nm near-ultraviolet (NUV) light activates the Pdots to catalytically produce hydrogen (H2). The generated H2 selectively scavenges cytotoxic reactive oxygen species (ROS), especially ·OH and •O2[-], and inhibits M1 macrophage polarization through modulation of the NOD-associated MAPK and AP-1 signaling pathways. As a result, it exerts potent anti-inflammatory and antioxidant effects. H2 generation, together with the oxidation by-products, further promotes the release of Ag[+], creating a self-propagating therapeutic cycle. In vivo studies using skin and liver infection models demonstrated accelerated wound closure, reduced inflammatory infiltration, enhanced angiogenesis, and improved tissue regeneration. Biocompatibility and biosafety tests further validated the hydrogel's potential for biomedical applications. The concept of "one material with three functions," integrating PTT, H2 therapy, and Ag[+]-mediated antimicrobial activity, enables precise, stage-specific, and microenvironment-responsive intervention. This approach highlights the potential of the hydrogel as a platform for smart wound management and clinical translation.

Bacterial infections, particularly those caused by multidrug-resistant pathogens and biofilm formation, have significantly undermined the efficacy of conventional antibiotics, highlighting the urgent need for novel antibacterial strategies. NIR-driven photothermal (PTT) and photodynamic therapies (PDT) have emerged as promising non-antibiotic approaches due to their noninvasive nature and precise spatiotemporal controllability. However, single-modality NIR treatments remain constrained by potential thermal damage to healthy tissues and reduced efficacy within the infection microenvironment. To address these limitations, researchers have developed NIR-mediated multimodal strategies that integrate complementary mechanisms for synergistic antimicrobial effects. Despite increasing studies, a systematic overview of NIR-based synergistic antibacterial strategies remains lacking. This review provides the first comprehensive focus on the combined application of NIR-mediated PTT/PDT with gas therapy (GT), chemodynamic therapy (CDT), immunotherapy, antibiotic adjuvants, and sonodynamic therapy (SDT). We summarize recent advances, discuss how these approaches overcome resistance, disrupt biofilm barriers, enhance antibacterial efficiency, and promote wound healing, and highlight the current challenges and prospects for clinical translation in this rapidly evolving field.

Indocyanine Green (ICG) is a widely used near-infrared fluorophore in biomedical imaging and therapy due to its strong light absorption and effective heat conversion abilities. Recently, combination of chemotherapy with PTT (chemo-PTT) has emerged as a promising approach to improve cancer treatment effectiveness. This study investigates the interaction between Noscapine Hydrochloride (Np.HCl), a benzyl isoquinoline alkaloid with potential anticancer effects, and ICG, with a specific focus on its influence on ICG's optical properties. The findings indicate that Np.HCl promotes J-aggregation even at low concentrations, with aggregation intensity increasing proportionally to Np.HCl concentrations. A simple and reproducible method has been developed to synthesize these J-aggregates (IJAs) using FDA-approved agents, Np.HCl and ICG, highlighting their potential applications in improving chemotherapy outcomes. Spectral analysis revealed the presence of both blue and red shifts, depending on the dye concentration, indicating molecular interactions between Np.HCl and IGs, which were quantitatively assessed through Gaussian fitting. Additionally, Stern-Volmer plots were used to analyze the quenching dynamics and interaction mechanism. Further, cytotoxicity studies have been performed on H1299 cells, which revealed IC50 values of 354.4 and 165.8 μM for ICG and Np.HCl, respectively. Notably, the combination treatment (ICG:Np.HCl) exhibited the highest cytotoxic effect, suggesting a potential synergistic interaction. This is the first demonstration of noscapine-driven ICG J-aggregation, creating a new scope for designing dye-drug assemblies with optical and therapeutic functions.

Recent attention has focused on bone's highly vascularized characteristics to improve bone defect repair, an interplay referred to as osteogenesis-angiogenesis coupling. Regarding this point, it is promising to utilize photothermal therapy (PTT) to enhance the coupling, with increasing research in the field. However, the application models, mechanisms, and therapeutic efficacy remain underexplored. Previous reviews have mainly addressed the general osteogenic applications of PTT. This review instead focuses on how PTT regulates the spatiotemporal coordination of osteogenesis and angiogenesis during bone repair. A comprehensive overview of the mechanisms underlying PTT is presented, together with a systematic summary of photothermal agents (PTAs) and their application strategies for enhancing osteogenesis and angiogenesis. Furthermore, the current concerns and challenges associated with the clinical translation of PTT are discussed. Finally, future perspectives and potential development directions are proposed, with the aim of offering new opportunities and innovative approaches for bone repair.

Cancer remains a major threat to global public health, highlighting the urgent need for precise and effective treatment strategies. Photothermal therapy (PTT) has gained increasing attention as a promising alternative owing to its non-invasiveness, deep tissue penetration, and oxygen-independent mechanism. However, the development of high-performance organic photothermal agents (PTAs) with pronounced near-infrared absorption, high photothermal conversion efficiency (PCE), and good photostability remains challenging. Herein, we propose a synergistic strategy combining π-bridge and donor engineering to design a series of aggregation-induced emission (AIE)-active small-molecule photosensitizers. Experimental and theoretical analyses reveal that stepwise introduction of a planar thiophene π-bridge and methoxy donor groups systematically regulates the excited-state energy dissipation pathways, enabling a continuous modulation from photodynamic therapy (IsoTPA), through balanced synergistic PDT/PTT (IsoTHTPA, PCE = 57.2%), to highly efficient PTT (IsoTHTO, PCE = 64.3%), which reveals the fundamental competitive interplay between intersystem crossing and non-radiative decay. Encapsulated into nanoparticles, IsoTHTO NPs demonstrate efficient photothermal ablation of 4T1 tumor cells and significant tumor growth inhibition under 660 nm laser irradiation both in vitro and in vivo. This work presents a reasonable molecular design approach for tunable access to PDT, synergistic PDT/PTT, and PTT modalities from a single molecular platform for cancer phototheranostics.

The effects of prolonged sedation on hematological, biochemical, and coagulation variables have not been previously investigated in veterinary medicine. Twelve healthy adult mixed-breed female dogs were included. Blood samples (6 mL) were collected at baseline (M0) for complete blood count (CBC), biochemical testing, prothrombin time (PT), activated partial thromboplastin time (PTT) and fibrinogen. After M0, dogs were allocated into two groups: midazolam-fentanyl-propofol group (MFG; n = 6), which received a continuous infusion of midazolam (0.5 mg/kg/h), fentanyl (10 µg/kg/h), and propofol (18 mg/kg/h); and ketamine-morphine-propofol group (KMG; n = 6), which received a continuous infusion of ketamine (0.6 mg/kg/h), morphine (0.26 mg/kg/h), and propofol (18 mg/kg/h). The infusion was maintained for 24 hours under mechanical ventilation. Laboratory parameters were reassessed from 12 to 24 hours after the beginning of infusion (M12 and M24), and at 12, 24, and 48 hours after the infusion (T12, T24, and T48). Both protocols significantly reduced erythrocyte count, packed cell volume, and haemoglobin concentration. In KMG, TTP decreased significantly at M12, M24, and T24; TSP at M24; and lymphocytes at M12 and M24. No significant changes were observed in ALP, ALT, albumin, globulins, creatinine, urea, glucose and blood coagulation. Triglyceride and cholesterol concentrations increased significantly from M6 to T48, but without biochemical evidence of hepatic, renal, or coagulation impairment. Overall, both protocols induced transient hematological and biochemical changes without clinically meaningful alterations in hepatic or renal function, supporting their use in healthy dogs mechanically ventilated for 24 hours.

Synergistic photodynamic and photothermal therapy (PDT/PTT) holds immense promise for cancer treatment, yet its efficacy is often compromised by limited photosensitizer performance, glutathione (GSH)-mediated ROS quenching, and tumor-protective autophagy. Herein, we developed a GSH-responsive hydrophilic porphyrin copolymer (PPS) that covalently integrates porphyrin into the polymer backbone, ensuring high loading capacity and minimal carrier-related toxicity. PPS exhibits robust absorption around 800 nm, enabling simultaneous PDT and PTT under a single NIR laser. By incorporating the autophagy inhibitor chloroquine (CQ), the resulting CQ@DPPS nanosystem achieves multi-modal synergy: intracellularly, CQ not only inhibits phototherapy-induced autophagic flux to suppress cell survival but also facilitates the lysosomal escape of photosensitizers, heightening programmed cell death via Bcl-2 inhibition and Caspase-3 activation. Crucially, CQ@DPPS significantly activates NK cell-mediated innate immune surveillance and enhances the secretion of granzyme B (GZMB) in NK cells by downregulating MHC-I expression on the surface of tumor cells. In vivo, CQ@DPPS combined with 808 nm irradiation achieved complete tumor regression in HCT116-bearing mice and significantly attenuated hepatic metastasis. This work provides a potent strategy to overcome phototherapy resistance through the integration of autophagy inhibition, dual-mode phototherapy, and innate immune activation. STATEMENT OF SIGNIFICANCE: Clinical translation of PDT/PTT therapy is hindered by inefficient photosensitizer delivery, GSH-mediated ROS depletion, and cytoprotective autophagy in tumors. Here, we report a GSH-responsive hydrophilic porphyrin copolymer with porphyrin covalently integrated into the polymer backbone, enabling high loading, reduced carrier burden, and effective 808 nm-triggered PDT/PTT. Co-delivery of CQ in the CQ@DPPS nanosystem not only suppresses protective autophagic flux, but also promotes lysosomal escape, mitochondrial apoptosis, and NK cell-mediated antitumor immunity through reduced MHC-I expression and increased GZMB secretion. This multi-mechanistic platform achieved complete tumor regression and reduced hepatic metastasis in vivo, offering a promising biomaterial strategy to overcome major barriers in phototherapy and facilitate clinical translation.