Electron-spin dynamics represent an additional dimension in enzymatic catalysis, where most regulatory strategies focus on modulating active-site chemistry. Here, we present a spintronic approach that employs chiral gold nanohelices (CAu) as electron spin polarizers to enantiospecifically modulate cyclooxygenase-2 (COX-2) activity for rheumatoid arthritis intervention. Exploiting the chirality-induced spin selectivity (CISS) effect inherent to both COX-2 and CAu, we demonstrate that left-handed CAu (Lh-CAu) enhances, whereas right-handed CAu (Rh-CAu) suppresses COX-2 catalytic efficiency via spin-dependent electron transfer at the chiral nanoparticle-enzyme interfaces. To achieve targeted modulation in complex biological settings, we engineer molecularly imprinted CAu (CAu@MIP) for selectively regulating COX-2 in inflammatory cells and collagen-induced arthritis murine model (male DBA/1 J mice). Treatment with Rh-CAu@MIP significantly reduces prostaglandin E2 secretion and mitigates joint inflammation, achieving therapeutic efficacy comparable to conventional COX-2 inhibitors. Our findings introduce electron spin polarization as an orthogonal mechanism for enzymatic regulation, offering a bioelectronic strategy for inflammation-targeted therapy.

Photodynamic therapy (PDT) efficiency of nanomaterials is typically enhanced through promoting electron-hole separation to generate reactive oxygen species (ROS), however, electron energy dissipation severely constrains ROS production and PDT performance, which is never recognized and addressed. Herein, we constructed narrowbandgap negative magnetoresistance nanoparticles (ZFO NPs), followed by in situ growth of gold nanodots (Au NDs) to form ZFO@Au NPs. Electrons were excited from ZFO NPs by near infrared (NIR) light and transported to Au NDs, achieving electron-hole separation. More importantly, electron spin polarization was simultaneously induced by external magnetic force (EMF), minimizing the energy dissipation from electron-hole, electronelectron and electron-lattice collisions. ZFO@Au NPs exhibited higher ROS production under combined NIR light and EMF treatments than either treatment, and further folate-modified ZFO@Au NPs confirmed the promising in vitro and in vivo therapeutic effects. This study reveals the significance of energy dissipation minimization in PDT, offering a new paradigm for material design.

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, characterized by progressive joint degradation, pain, and diminished mobility, all of which collectively impair patients' quality of life and escalate healthcare expenditures. Current treatment options are often inadequate due to limited efficacy, adverse side effects, and temporary symptom relief, underscoring the urgent need for more effective therapeutic strategies. Recent advancements in nanomaterials and nanomedicines offer promising solutions by improving drug bioavailability, reducing side effects and providing targeted therapeutic benefits. This review critically examines the pathogenesis of OA, highlights the limitations of existing treatments, and explores the latest innovations in intelligent nanomaterials design for OA therapy, with an emphasis on their engineered properties, therapeutic mechanisms, and translational potential in clinical application. By compiling recent findings, this work aims to inspire further exploration and innovation in nanomedicine, ultimately advancing the development of more effective and personalized OA therapies.

Piezoelectric, conductive, and injectable hydrogel (SPG hydrogel) is constructed to rapidly close wounds, efficiently harvest biomechanical energy from animal motion, and generate electrical stimulation for electrotherapy of wound healing. 3-amino-4-methoxybenzoic acid (AMB) monomer was polymerized and grafted onto the gelatin, which was further crosslinked using EDC/NHS and embedded with strontium titanate nanoparticles (80.5 wt%), forming SPG hydrogel. This SPG hydrogel had high tissue adhesion ability, and could generate the output voltage (maximum output voltage 1 V) and current (maximum output current 0.5 nA) upon mechanical bending, promoting NIH-3T3 cell migration and proliferation. Upon application to the mice wound model, the SPG hydrogel rapidly closed the skin wound, smoothed the wound's appearance, reduced the remaining wound size, and increased epidermal thickness, demonstrating remarkable wound healing capabilities. This study suggests that the body motion-promoted electrotherapy offers a promising strategy for wound healing. Statement of Significance Piezoelectric nanomaterials are often incorporated into hydrogels to create piezoelectric hydrogels for wound healing. However, piezoelectric nanomaterials tend to agglomerate within the hydrogel matrix, and the hydrogel's low conductivity hinders efficient electron transfer. Together, both factors significantly reduce the piezoelectric effect. In this study, we developed an SPG hydrogel to improve the homogeneity and conductivity of the piezoelectric hydrogel. We first designed a conductive PG hydrogel and then immoblized piezoelectric STO nanoparticles within its matrix through coordination chemistry. Upon mechanical deformation, the uniformly distributed STO nanoparticles can generate electricity, which can efficiently transfer through the conductive matrix to the hydrogel's surface. This design shows great potential for wound healing applications.

The transition between the inflammatory phase and the proliferative phase is critical for wound healing. However, the development of proper switchers that can regulate this transition is facing great challenges. Macrophages play versatile roles in all wound healing phases because they can readily switch from pro-inflammatory M1 phenotypes to anti-inflammatory M2 phenotypes in response to different microenvironment stimuli. Herein, taking advantage of enhanced electron transfer by coupling MoS2 with a highly conductive activated carbon fiber (ACF) network, a MoS2-ACF heterojunction structure was constructed as a macrophage M1-M2 phenotype switcher (MAPS) for regulating inflammation-proliferation transition to accelerate wound healing. In the early stages of wound repair, MAPS-mediated photothermal effects with near-infrared laser irradiation could promote macrophage reprogramming to the M1 phenotype, which can expedite inflammation. NIR photo-induced hyperthermia, together with M1 macrophages, directly and indirectly kills bacteria. Later, during the healing process, the MAPS could further reprogram macrophages towards the M2 phenotype via its inherent reactive oxygen species (ROS) scavenging ability to resolve inflammation, promoting cell proliferation. Therefore, MoS2-ACF heterojunction structures provide a new strategy to modulate inflammation-proliferation transition by rebalancing the immuno-environmental equilibrium of macrophage M1/M2 phenotypes.

Pre-metastatic niche (PMN) in the distant organs provides a suitable soil for the colonization of circulating tumor cells (CTCs). Targeting PMN destruction is becoming an effective strategy against tumor metastasis. Considering that the lung is the organ with the highest incidence of melanoma metastasis, nebulized inhalation can directly deliver drugs to the lung. Herein, M1 macrophage-derived, CXCR4-overexpressed, and BMS202-loaded extracellular vesicles (BMS@C-M1 EV) were constructed to inhibit postoperative melanoma lung metastasis. After nebulized inhalation, BMS@C-M1 EV effectively accumulated in the lungs of postoperative melanoma mice, its surface CXCR4 could inhibit the recruitment of monocytic myeloid-derived suppressor cells (mo-MDSCs) by consuming CXCL12, and its M1 pro-inflammatory feature repolarized tumor-associated macrophages (TAMs) from the M2 pro-tumor phenotype into the M1 antitumor phenotype, thereby reversing the immunosuppressive microenvironment, activating the T cell immune response, and preventing PMN construction. Furthermore, BMS202 released by BMS@C-M1 EV could induce the dimerization of PD-L1 in CTCs to block the PD-1/PD-L1 interaction, thereby enhancing T cell-mediated immune elimination of CTCs and further inhibiting the occurrence of metastasis. Therefore, BMS@C-M1 EV through nebulized inhalation could disrupt PMN formation and eliminate CTCs in the lung, effectively suppressing postoperative melanoma lung metastasis. This therapeutic approach holds great potential for preventing postoperative melanoma lung metastasis.

In situ cancer vaccines that utilize the body's own tumor-associated antigens (TAAs) to induce tumor-specific adaptive immune responses are emerging as a promising strategy in cancer therapy. However, the rapid clearance of TAAs due to innate immune system hinders the development of effective antitumor immunity. To address this challenge, we developed a nanomotor system (DDMSN@MOMVPF) as an in situ cancer vaccine capable of chemotactically capturing TAAs, significantly inhibiting the rapid clearance of TAAs and enhancing cancer immunotherapy. In response to acid tumor microenvironment, DDMSN@MOMVPF exfoliated folate acid-attached, mitoxantrone-embedded bacterial outer membrane vesicle (OMV) fragments, which could be specifically taken up by tumor cells to induce immunogenic cell death (ICD) and release DNA-associated TAAs. Subsequently, the exposed DNase on DDMSN@MOMVPF detected DNA gradient and propelled nanoparticles chemotactically capturing TAAs. In vivo results indicated that DDMSN@MOMVPF suppressed both primary and distant tumors and elicited immune memory effects to prevent tumor recurrence.

Cancer immunotherapy is developing as the mainstream strategy for treatment of cancer. However, the interaction between the programmed cell death protein-1 (PD-1) and the programmed death ligand 1 (PD-L1) restricts T cell proliferation, resulting in the immune escape of tumor cells. Recently, immune checkpoint inhibitor therapy has achieved clinical success in tumor treatment through blocking the PD-1/PD-L1 checkpoint pathway. However, the presence of M2 tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) will inhibit antitumor immune responses and facilitate tumor growth, which can weaken the effectiveness of immune checkpoint inhibitor therapy. The repolarization of M2 TAMs into M1 TAMs can induce the immune response to secrete proinflammatory factors and active T cells to attack tumor cells. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were prepared for reprogramming M2 TAMs into M1 TAMs. BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes. The formed biomimetic FBN@M could produce gaseous carbon dioxide (CO2) from NaHCO3 in response to the acidic TME, breaking up the macrophage membranes to release BMS-202. A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment.

Bladder cancer is one of the most common clinical malignant tumors with a high recurrence rate after surgery. To improve the therapeutic effect, intravesical instillation of chemotherapeutic drugs is usually applied after surgery. However, due to the unique microenvironment in the bladder, the drug concentration is usually rapidly reduced with urinary excretion, leading to low accumulation in bladder cancer and poor therapeutic effect. Cellular microvesicles (MVs) have parental cell-specific characteristics and hold homologous targeting and adhesion abilities to their parent cells, achieving efficient cell uptake in their parent cells. In this study, pirarubicin (THP), a clinically approved intravesical chemotherapeutic drug, is encapsulated into bladder cancer cell-derived MVs to form THPMVs, which have high targeting and adhesion abilities to bladder cancer and facilitate intravesical therapy of bladder cancer. The results show THPMVs compared with free THP exhibited higher cellular uptake in MB49 bladder cancer cells and cause more significant apoptotic cells. After intravesical instillation into a bladder cancer mouse model, THPMVs can significantly accumulate in bladder cancer tissues, and cause an obvious reduction in bladder weights and volumes, exhibiting promising therapeutic effects. Homologous targeting and adhesion abilities of THPMVs greatly contribute to the intravesical therapy of bladder cancer. Pirarubicin (THP) is encapsulated in bladder cancer cell-derived microvesicles (MVs) to form THPMVs, exhibiting higher cell uptake in bladder cancer cells compared with normal cells due to homologous targeting and adhesion characteristics of MVs. After intravesical instillation, THPMVs can significantly accumulate in bladder cancer tissue and show promising therapeutic effect.image

Rheumatoid arthritis (RA) is a common chronic inflammatory disease capable of causing the disability. Although various antioxidant strategies have been attempted for prevention and treatment of RA through scavenging the free radicals, the therapeutic effect is limited. Recently, it is reported that the unremitting course of RA intensely correlates with the persistence of immunologic memory, in which the imbalance of T helper 17 (Th17) cells/regulatory T (Treg) cells plays an important role. Herein, we constructed Janus mesenchymal stem cell (MSC)-hitchhiked melanin nanoparticles (MSCFM) for RA therapy, where one half of MSC kept intact for chemotactically migrating towards the RA inflammatory sites and efficiently restoring the Th17/Treg balance based on the property of MSCs, while the other half hitchhiked the iron-doped melanin (FM) nanoparticles (NPs) and release them to scavenge free radicals for maintaining the durability of Th17/Treg balance. In vitro studies indicated MSCFM could migrate towards CXCL12 inflammatory cytokine, scavenge reactive oxygen and nitrogen species, inhibit Th17 cell proliferation and induce Treg cell production. Further in vivo studies corroborated that intravenously injected MSCFM could target the RA site of collagen-induced arthritis mouse model and alleviate the pathological progression of RA. MSCFM holds great potential as an anti-inflammatory agent for RA management.

Reprogramming of tumor associated macrophages (TAMs) from M2 to M1 phenotype is becoming a feasible strategy for tumor immunotherapy, however, its efficacy is potentially constrained by the acellular components of immunosuppressive tumor microenvironment (TME). Herein, hollow MnO2 (HMnO2) nanoparticles were loaded with autophagy inhibitor chloroquine (CQ), carried both lactate oxidase (LOX) and glucose oxidase (GOX) on their surface, and further were camouflaged with tumor cell membrane, forming the final mCMLG nanoparticles for TME immunostimulation. After intravenous injection, mCMLG nanoparticles effectively accumulated in the tumor area and were taken up by tumor cells. Under the acidic conditions, MnO2 reacted with endogenous hydrogen peroxide (H2O2) to generate O2 and Mn2+, resulting in the exposure of LOX and GOX as well as the release of CQ. The exposed enzymes reduced the level of lactate (a predominant acellular component), alleviating the inhibition on TAM reprogramming; hydroxyl radical (·OH) generated by Fenton-like reaction of Mn2+ could directly promote this reprogramming, thus effectively facilitating the reprogramming of TME from immunosuppressive to immunostimulatory. Moreover, ·OH also induced chemodynamic therapy (CDT) effect against tumor cells, which was further amplified by CQ. This study corroborates that mCMLG nanoparticles can effectively inhibit tumor growth through the enhanced immunotherapy and CDT.

Acute kidney injury (AKI) is a heterogeneous, high-mortality clinical syndrome with diverse pathogenesis and prognosis, but it lacks the effective therapy clinically. Its pathogenesis is associated with production of reactive oxygen/nitrogen species and infiltration of inflammatory cells. To overcome these pathogenic factors and improve the therapeutic efficiency, we synthesized triptolide-loaded mesoscale polydopamine melanin-mimetic nanoparticles (MeNP4TP) as the antioxidant plus anti-inflammatory therapeutic platform to synergistically scavenge reactive oxygen/nitrogen species (RONS), inhibit the activity of macrophages and dendritic cells, and generate Treg cells for AKI therapy. It was demonstrated that mesoscale size was beneficial for MeNP4TP to specifically accumulate at renal tubule cells, and MeNP4TP could significantly attenuate oxidative stress, reduce proinflammatory immune cells in renal, and repair renal function in cisplatin-induced AKI mouse model. MeNP4TP might be a potential candidate to inhibit oxidative damages and inflammatory events in AKI.

Significance Short-cavity single-frequency fiber lasers and high-repetition-rate passively mode-locked fiber lasers based on high-gain rare-earth (RE)-doped fibers have significant applications in the manufacturing, healthcare, and military fields. Although RE-doped silica fibers have advantages such as low propagation loss and easy splicing, the low fiber unit gain coefficient caused by the low doping concentration of RE ions severely limits the performance of short-cavity lasers. In recent years, with the expansion of fundamental research on RE-doped silica glasses and significant improvements in fiber fabrication techniques, RE-doped silica fibers have been developed and successfully applied for short-cavity lasers. The performance of short-cavity lasers at various wavelengths has been significantly improved, unleashing their potential for application. Considering fiber fabrication techniques and short-cavity laser applications using different RE-doped silica fibers, this review systematically analyzes the latest developments and application progress of highly RE-doped silica fibers and predicts their future development. Progress Owing to the continuous improvement of fiber fabrication techniques and the further development of basic research on RE-doped silica glasses, the doping concentration of RE ions and the pump absorption coefficient of silica fibers have been significantly improved in recent years. Table 4 lists the high absorption coefficient Nd3+,Yb3+, Er3+, and Tm3+-doped silica fiber products developed by special fiber manufacturers such as Nufern, Coractive, and Liekki. The most typical is the Coractive Yb406 Yb3+-doped silica fiber, which has a core absorption coefficient of 2400 dB/m at 976 nm. According to estimation, the Yb doping content (mass fraction) in the core can reach 5 % (or even higher), which is significantly higher than the Yb doping content (mass fraction) of conventional Yb3+-doped silica optical fibers (similar to 1 %). Taking these high-absorption RE-doped silica fibers as gain media, many research groups have successfully demonstrated their applications in short-cavity single-frequency and high-repetition-rate mode-locked fiber lasers with wavelengths ranging from the 0.9 to 2.0 mu m bands. For instance, in the 0.9 mu m wavelength band, the research team from the Shanghai Institute of Optics and Fine Mechanics successfully developed a highly Nd3+-doped silica single-mode fiber with a 4.1 dB/cm pump absorption coefficient. The research team demonstrated DBR single-frequency lasers at 890-910 nm based on this fiber, extending the single-frequency laser of RE-doped silica fibers to below 900 nm (Fig. 11). Additionally, they also demonstrated an over 200 MHz high-repetition-rate passively mode-locked laser at 920 nm with an F-P cavity structure (Fig. 12). In the 1.0 mu m wavelength band, in 2023, a research team from Tianjin University realized a high-efficiency 1064 nm single-frequency DBR fiber laser using the above mentioned Coractive Yb406 fiber. The slope efficiency reached 66.4 % with only a 1.2 cm Yb3+-doped fiber (Fig. 13), which is the highest efficiency recorded for short-cavity single-frequency lasers using Yb3+-doped silica fibers. This efficiency is comparable to that of high-gain Yb3+-doped phosphate fiber, indicating that the fabrication technique for high-doping-concentration RE-doped silica fibers has been significantly improved. In the 1.5 mu m wavelength band, in 2021, the research team from Shandong University conducted studies on a high-repetition-rate passively mode-locked laser using a commercial highly Er3+-doped silica fiber (Liekki-Er110-4/125). Through in-depth analysis of SESAM (semiconductor saturable absorber mirror) parameters and experiments, they noted that an SESAM with a smaller modulation depth was better for high-repetition-rate passively mode-locked lasers. After optimization, they realized a 5 GHz fundamental-repetition-rate passively mode-locked laser at 1.5 mu m using only a 2.0 cm Liekki-Er110 fiber as the gain medium (Fig. 20). In the 2.0 mu m wavelength band, in 2024, a research team from the University of Adelaide in Australia realized single DBR fiber lasers at 1908 nm, 1950 nm, 1984 nm, and 2050 nm, using a custom high-absorption 5/125 Tm3+-doped silica fiber from Coherent. The numerical aperture of the fiber core is 0.21, and the absorption coefficient at 1540 nm is 195 dB/m +/- 6 dB/m. The length of the Tm3+-doped silica fiber is 25 mm. The slope efficiencies corresponding to the 1908 nm, 1950 nm, 1984 nm, and 2050 nm bands are 33 %, 37 %, 48 %, and 26 %, respectively (Fig. 22). Among them, the direct output power from the cavity at 1984 nm exceeds 1 W. The efficiency and power at 1984 nm are currently the highest recorded for a DBR single-frequency laser at a wavelength of 2.0 mu m. Conclusions and Prospects RE-doped specialty optical fibers are crucial components of fiber lasers. For short-cavity fiber lasers, the performance of RE-doped fibers directly determines the laser parameters, including laser efficiency, wavelength, and repetition rate. As indicated above, highly RE-doped silica fibers are being increasingly applied in short-cavity lasers in the 0.9-2.0 mu m bands. Although some laser parameters obtained from RE-doped silica fibers are still worse than those from RE-doped soft glass fibers, the performance gap between RE-doped silica fibers and RE-doped soft glass fibers is constantly narrowing, indicating the application feasibility of RE-doped silica fibers in short-cavity lasers. However, we note that the fabrication techniques of highly RE-doped silica fibers are mainly mastered by international manufacturers such as Liekki, Nufern, and Coractive, and in comparison, domestic research and fiber product development are lagging behind and require further breakthroughs. For the application of single-frequency narrow-linewidth and high-repetition-rate mode-locked fiber lasers, further research on highly RE-doped silica fibers can be conducted considering two aspects: further improvement of the performance of highly RE-doped silica fibers and short cavity lasers and the regulation of the fiber gain spectrum.

The large recruitment of tumor-associated macrophages and low exposure of tumor-associated antigens in tumor microenvironment have severely suppress the efficacy of anti-tumor immunotherapy. Herein, biosynthesized magnetosome (Mag) from bacteria was loaded with photothermal/photodynamic agent/near infrared (NIR) fluorescence dye (IR780) and further modified with lipid-PEG-c(RGDyK) through biomembrane, forming IMagRGD for fluorescence imaging, magnetic resonance imaging, immunotherapy and photodynamic/photothermal therapy. After intravenous injection into B16F10 tumor-bearing mice, IMagRGD could efficiently accumulate in tumor tissues based on near infrared (NIR) fluorescence and magnetic resonance dual-modality imaging, and repolarize tumor-associated macrophages (TAMs) from M2 phenotype to M1 phenotype, significantly improving the effect of tumor immunotherapy. Moreover, photothermal and photodynamic effect of IR780 could kill tumor cells and elicit immunogenic cell death to mediate anti-tumor immunity, promoting dendritic cells (DCs) maturation and then activating specific effector T cells to further eliminate tumor cells. This study provides a new approach for reversing the activity of tumor immunosuppressive microenvironment and strengthening the efficiency of tumor photoimmunotherapy.

Wound healing is a complex and orchestrated physiological process that involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling stages. Various nanomaterials have been developed to improve the wound healing; however, most of them can only promote an individual stage of this intricate process, lacking hierarchical acceleration for multiple stages. In the present study, spiky gold-palladium heterostructured nanoparticles (AuPd SHs) were designed to possess topographical architectures on the surface of nanoparticles, capable of promoting multistage wound healing in a programmable manner. First, the spiky surface topography of AuPd SHs exhibited the potent nanobridge effect for rapid wound closure, promoting the hemostasis stage. Second, the heterostructures of AuPd SHs realized visible-light-mediated hot electron excitation and electron–hole spatial separation between Au cores and Pd spikes to efficiently generate reactive oxygen species, beneficial for the inflammation stage. Third, the spiky surface topography of AuPd SHs triggered macrophage polarization from M1 to M2 phenotype, promoting the proliferation and maturation stages. Spiky AuPd SHs with simple composition and compact structures exhibit hierarchical acceleration on multiple stages of wound healing.

Fluorescent powders exhibiting excitation dependence and luminescent discoloration are profoundly relevant for concealing information and enhancing optical antiforgery protection. In this study, Bi3+/Ln3+ (Eu3+, Er3+)-doped phosphors exhibiting multicolor luminescence and excitation wavelength dependence were synthesized. The Bi3+/Eu3+-codoped phosphors emitted blue, pink, lavender, and red lights under excitation from conventional ultraviolet (UV) sources. In addition to emitting blue light, the Bi3+/Er3+-codoped phosphors also transmitted upconversion-emission light from green to yellow under 980-nm laser excitation. Additionally, the luminous color of the Ca3Y2Ge3O12:0.01Bi3+, 0.2Er3+ phosphor changed from yellow to orange as the temperature increased. Combining the above luminous-color-change phenomena, the word-hiding experiment exhibited excellent realistic information hiding, with complex color transformation in the stamen and petal parts of the flower pattern. Furthermore, rapid multimodal and complex discoloration was achieved using easy-to-obtain light sources, confirming the potential of Bi3+/Ln3+ phosphors for anticounterfeiting applications.

To simulate the effects of ionizing irradiation on photo-thermo-refractive (PTR) glass in a cosmic environment, the optical properties changes under ionizing irradiation (γ-, X- and UV-ray) were investigated on PTR-glass with and without Ag doped (named as PTR-S and PTR-F, respectively) samples. Thermoluminescence (TL), transmission electron microscopy (TEM) measurements, UV-VIS absorption spectroscopy analysis, Gaussian peak fitting, and continuous wave electron paramagnetic resonance (CW-EPR) were used to determine the species of the irradiation-induced color centers. The radiation resistance properties of the Ag-species on the PTR-S glass were evaluated by comparing the defect center concentrations in the irradiated PTR-S and PTR-F glasses. The results showed that absorption in PTR-F and PTR-S glass increased significantly with increasing γ-irradiation dose, which was related to HC1, HC2, E′, L, ETC defect centers and Ag-species, and the formation of HC1, HC2, E’, and L-centers was reduced by the doping of Ag into the PTR-S glass matrix. Compared with the γ-irradiation, X-irradiation showed a similar effect. In comparison, UV-irradiation induced fewer defect centers and smaller Ag (NPs). This discrepancy could be caused by variations in photon energies.

Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.

Premetastatic niche (PMN) is a prerequisite for tumor metastasis. Destruction of PMN can significantly suppress the tumor metastasis. Bone marrow-derived cells are usually recruited into the premetastatic organs to support PMN formation, which can be orchestrated by tumor-derived secreted factors. Neutrophils can chemotactically migrate towards the inflammatory sites and consume tumor-derived secreted factors, capable of acting as therapeutic agents for a broad-spectrum suppression of PMN formation and metastasis. However, neutrophils in response to inflammatory signals can release neutrophil extracellular traps (NETs), promoting the tumor metastasis. Herein, live neutrophils are converted into dead neutrophils (CNE) through a quick-frozen process to maintain PMN-targeting and tumor-derived secreted factor-consuming abilities but eliminate NET-releasing shortcomings. Considering macrophages-regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) are further hitchhiked on the surface of CNE to form CNEMag, which can repolarize macrophages from M2 to M1 phenotype for further disruption of PMN formation. A series of in vitro and in vivo assessments have been applied to confirm the effectiveness of CNEMag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti-metastatic therapy in clinics.

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.