Reliable quantification of ascorbic acid (AA) is essential for pharmaceutical quality control. Herein, we report Fe-doped carbon dots (Fe-CDs) as a fluorescent nanozyme for the colorimetric/fluorometric dual-mode quantification of AA. Fe doping endows CDs with intrinsic peroxidase-like activity to catalyze H2O2-mediated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB), quenching the fluorescence of Fe-CDs via the inner filter effect. The introduction of AA reduces the oxTMB and leads to a decrease in absorbance and recovery of fluorescence. Such Fe-CD based dual-mode method achieves high sensitivity for AA quantification with a limit of detection of 89.1 ng mL-1 for the colorimetric mode and 90.9 ng mL-1 for the fluorometric mode, and exhibits satisfactory quantification accuracy in commercial AA tablets, demonstrating its applicability as a reliable, sensitive, and point-of-need tool for quality control of pharmaceutical tablets.

Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds remain difficult to treat because bacterial persistence, inflammation, antimicrobial resistance, and poorly controlled local toxicity can jointly impair tissue repair. Herein, we report an infection-responsive KCoF3@Fe-HA hydrogel that integrates potassium cobalt fluoride (KCoF3) with an Fe3+-crosslinked hyaluronic acid (HA) network for localized Co/Fe dual Fenton-like antibacterial therapy. Notably, the use of KCoF3 in antibacterial wound dressing systems has not yet been reported. In this design, KCoF3 serves as a confined Co reservoir, while the Fe-HA network provides catalytic Fe species and a biodegradable hydrogel matrix. The introduction of Co-mediated Fenton-like activity may broaden the effective catalytic pH range and compensate for the limited activity of Fe-based Fenton-like systems under infection-relevant weakly acidic conditions. Meanwhile, the HA network provides infection responsiveness, allowing weak acidity and bacteria-associated hyaluronidase to promote localized network relaxation and degradation. Together with the reservoir-like KCoF3 structure, this design enables sustained Fe/Co release around infected tissues, helping to maintain local antibacterial activity while reducing burst Co exposure and unnecessary metal leakage. KCoF3@Fe-HA showed stronger Fenton-like catalytic activity than single-metal hydrogel systems. The hydrogel exhibited broad-spectrum antibacterial activity against MRSA, Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) and effectively reduced bacterial burden in an MRSA-infected full-thickness wound model. Wounds treated with KCoF3@Fe-HA closed faster and showed weaker inflammatory signals, greater collagen deposition, and increased angiogenesis. Cytocompatibility, hemolysis, blood analysis, and major-organ histology supported its preliminary biosafety. This work provides a localized Co/Fe Fenton-like dressing strategy for antibiotic-free MRSA-infected wound healing, presenting KCoF3 as a confined Co reservoir integrated with an infection-responsive HA hydrogel network.

The bacterial cuproptosis-like death presents a promising strategy against antibiotic-resistant infections, yet its efficacy remains constrained by the insufficient influx of copper ions into bacteria. Inspired by the role of disulfiram (DSF) in disrupting copper homeostasis, we herein present an injectable hydrogel-based therapeutic system featuring DSF-enhanced bacterial cuproptosis-like death, synergistically combined with chemodynamic therapy (CDT), which demonstrated enhanced efficacy against methicillin-resistant Staphylococcus aureus (MRSA) in both in vitro and in vivo models. Meanwhile, the underlying mechanism of DSF-enhanced bacterial cuproptosis-like death was explored at the transcriptional level. Moreover, the developed hydrogel fostered a pro-healing microenvironment by promoting angiogenesis, collagen deposition, and fibroblast proliferation in a mouse model of the MRSA-infected wound. This hydrogel-based DSF-enhanced bacterial cuproptosis-like death provides a synergized strategy for treating antibiotic-resistant infected wounds.

Nanozyme-mediated catalytic therapy has emerged as a promising strategy for antitumor treatment, but it is imperative to further improve the catalytic efficiency of nanozymes to achieve potentiated antitumor efficacy. Single-phase high-entropy (HE) nanozymes with desirable enzyme-like catalytic activity and photothermal properties are appealing for enhancing the efficacy of catalytic therapy but have remained synthetically challenging. As a proof-of-concept demonstration, we herein prepared a single-phase HE Prussian blue analogue (HEPBA) using a conventional coprecipitation method. The HE mixing state enabled an exceptionally high photothermal conversion efficiency of 95.3% and a notable photothermally enhanced peroxidase-like catalytic activity. Therefore, the HEPBA-mediated photothermally enhanced catalytic therapy led to potentiated antitumor efficacy in both 4T1 and CT26 tumor-bearing mouse models. Thus, this work provides a rational and flexible platform for convenient and green preparation of biocompatible HE nanozymes and offers new perspectives on the use of HE nanozymes to improve the efficacy of catalytic therapy.

Proteolysis targeting chimeras (PROTACs) represent a cutting-edge approach for targeted protein degradation in cancer therapy, yet they face challenges such as poor pharmacokinetics and specificity issues, leading to undesirable off-target effects and limited antitumor potency. To address these issues, we introduce dual-targeted unimolecular theranostic probes (e.g., radioactive 177Lu-P-A and its cold counterpart natLu-P-A) for disease-activatable PROTACs in combination with targeted radionuclide therapy (TRT) against prostate cancer with high specificity and effectiveness. The probes achieve a cathepsin B (CTSB)-activatable pro-PROTAC moiety for precise degradation of bromodomain-containing protein 4 (BRD4) and a prostate-specific membrane antigen (PSMA)-targeted 177Lu-based TRT. Owing to the favorable pharmacokinetics and PSMA-mediated excellent targeting efficiency, the probe possesses high tumor imaging specificity and accumulation capacity of therapeutic units for highly effective PROTACs and TRT. In contrast, the free PROTACs unit (e.g., ARV-771) shows no observable therapeutic effect due to its poor targeting ability. Importantly, the BRD4 proteolysis by PROTAC activation can downregulate radiosensitivity-associated RAD51AP1 expression, synergistically enhancing the TRT effect and promoting apoptosis after combined therapy compared to individual treatment regimes. Additionally, the probe demonstrates high renal clearance, underscoring its biosafety for potential clinical translation. This study presents a potential approach for precise PROTACs combined with TRT for effective tumor therapy.

A qPBA nanocube-based HEzyme as a photothermal-adjuvant ICD-driven in situ nanovaccine was developed for potentiated tumor immunotherapy via ROS amplification and TAM repolarization.

Development of biomolecules coordinated iron ions-based Fenton agents is highly desirable for chemodynamic therapy in term of demanded biocompatibility and enhanced Fenton activity at tumor microenvironmental pH of 6.5. Herein, phycocyanin (PC), the only FDA-approved natural coloring agent, was selected to coordinate with iron ions. The spectroscopic investigations disclosed that PC displayed pH-dependent spectral and conformational responses upon addition of Fe ions. As a result, the effective formation of Fe-PC coordination merely occurred at pH 7 due to a less folded polypeptide matrix of PC. The formed Fe-PC coordination exerted an enhanced Fenton activity at pH 6.5 as attested by 3, 3', 5, 5'-tetramethlbenzidine assay and steady-state kinetic analysis. These findings not only provide fundamental insights of Fe-PC coordination but also highlight the potential biomedical significance of Fe-PC for severing as an effective Fenton agent in chemodynamic therapy.

Type I photodynamic therapy (PDT), which utilizes type I photoreactions and is less O-2-dependent, is expected to exert ideal synergistic therapy performance when combined with targeted radionuclide therapy (TRT). However, this combination has been less explored. To achieve it, this study presents a sequentially dual-targeted molecular theranostic probe for combining TRT and antihypoxic activatable PDT against prostate cancer. The probe achieves prostate-specific membrane antigen (PSMA)-mediated lock-and-key targeting ability and monoamine oxidase A (MAO-A) hydrolysis with activated fluoro-photoacoustic signals and O-2 (center dot-) generation. The PSMA motif not only enhances the targeting specificity but also increases the intracellular accumulation capacity of probe and promotes more MAO-A activation. In this regard, an enhanced inhibition of tumor growth is obtained for combined activatable antihypoxic PDT and TRT in comparison to any single regimen, including the commercial Lu-177-PSMA-617, thereby demonstrating the effective antitumor effect. This study provides a potential solution for a combination of TRT and PDT for effective tumor therapy.

Cuproptosis synergized with immunogenic cell death (ICD) triggered immunotherapy offers huge potential in addressing the limitations of current tumor therapies. However, the sensitivity of cuproptosis immunotherapy is severely restricted by multiple resistances derived from tumor microenvironment (TME). Herein, the Toll-like receptor agonist CpG templated copper sulfide loaded with disulfiram (DSF/CuS-C) was designed as a TME-reprogrammable cuproptosis nanoinducer for sensitizing tumor cell cuproptosis and simultaneously augmenting ICD driven anti-tumor immunity. The initiation of a sensitized cuproptosis via DSF/CuS-C mediated repolarization of M2 phenotypic macrophages with an assistant with photothermal effect was evidenced by the increased level of aggregation of lipoylated mitochondrial proteins and proteotoxic stress, which eventually resulted in a robust anti-tumor immune response for effectively eradating the breast tumor on a mouse model. The TME activated cuproptosis nanoinducer thus represents a novel and effective strategy for cooperatively reinforcing cuproptosis and anti-tumor immune response, holding great promise for innovation in the field of breast cancer treatment.

Neoadjuvant immunotherapy is superior to adjuvant immunotherapy in terms of immune suppression relief and antitumor immunity activation but inevitably suffers from immune-related toxicities. To minimize the toxic side effects, a local metronomic mild-temperature photothermal therapy (PTT) is proposed herein as a neoadjuvant immunotherapy. It was disclosed that the Prussian blue nanoparticle (PBNP)-mediated metronomic mild-temperature PTT effectively inhibited the growth of both primary and distal tumors on 4T1 xenograft tumor-bearing mice by effectively reversing the immunoimpressive TME through repolarizing M2-like TAMs to tumoricidal M1-like ones. Synergistically, the reprogrammed M1-like phenotype upregulated the percentage of cytotoxic T lymphocytes in the spleen and tumor, leading to an activated systemic immunity. This together with the demonstrated biosafety underscores the great potential of PBNP-mediated metronomic mild-temperature PTT as immunotherapy for reducing tumor burden presurgery and preventing tumor reoccurrence and metastasis postsurgery with minimized side toxic effects.

Phycocyanin (PC) holds significant potential for application in food production and biomedicine. Nevertheless, the stability and antioxidant activity of PC are influenced by pH. Improving the stability of PC under various pH conditions is thus highly demanded. Herein, N-isopropyl acrylamide (NIPAM) and chitosan were used to prepare poly(NIPAM-co-chitosan) (PNC) nanohydrogels for encapsulation PC, aiming to mitigate the adverse effect of pH on the stability and antioxidant activity of PC. The stability and antioxidative activity of PC encapsulated in PNC nanogels were evaluated at different pH values by determining the pigment retention rate (PRR) and free radical scavenging ability, respectively. The results demonstrated that the PNC encapsulation improved the stability and antioxidant activity of PC.

Due to the brilliant blue color and antioxidative activity, phycocyanin (PC) has gained increased attentions in various fields. However, its high sensitivity towards environmental stress has greatly hindered the application of this elegant natural product. Incorporation of PC in a particulate form is an attractive strategy to maintain its functionalities. Herein, biomimetic mineralization was applied to fabricate PC@calcium phosphate (CaP) microparicles. The stability and antioxidative activity of PC@CaP was evaluated. It was disclosed that PC@CaP exhibited an enhancement in stability and antioxidative activity under environmental stress, signifying the role of the biomimetic mineralization in maintaining the stability and antioxidative activity of PC for its potential use in a variety of fields with high added-value.

Therapeutic vaccine becomes a promising strategy to fight cancer by enhancing and sustaining specific anti-tumor immune responses. However, its efficacy is often impeded by low immunogenicity, the immunosuppressive tumor microenvironment (TME), and immune-related adverse events. Herein, we introduce 1-tetradecanol (TD)-wrapped, CpG-loaded porous Prussian blue nanoparticles (pPBNPs-CpG@TD) as a nanoimmunomodulator to initiate photothermal-induced immunogenic cell death (ICD) and photothermal-responsive release of CpG for augmenting the ICD effect. It was revealed that the dual-photothermal action significantly potentiated the in situ anti-tumor vaccine-like immunotherapy in terms of enhanced immunogenicity, promoted dendritic cell maturation, and increased T lymphocyte infiltration, consequently eliciting a robust immune response for inhibiting both primary and rechallenge tumors on a subcutaneous 4T1 tumor-bearing mouse model. The development and use of photoactive nanoimmunomodulators represents a novel and effective strategy to boost immunogenicity and counteract immunosuppressive TME, marking a significant advancement in the realm of ICD-driven in situ anti-tumor vaccine-like immunotherapy.

Nanozymes mediated chemodynamic therapy (CDT) is a newly developed therapeutic modality with high specificity. The efficacy of CDT, however, still confronts challenges from the immune inhibitory tumor microenvironment (TME). It is thus of great significance to synergize CDT with immunotherapeutic interventions. Herein, this work reports the design and preparation of CpG loaded, Cu2+ doped double layered hydroxides nanosheets (CpG/Cu-LDHs) as immuno-nanozymes to potentiate overall anti-tumor efficacy by synergizing CDT with immunogenic cell death (ICD)-activated local and systemic immune responses. Such cooperative CDT-immuno effect together with immunosuppressive TME remodeling capacity conferred by CpG/Cu-LDHs led to effective suppression of both treated primary tumor and untreated distant tumor on a mouse tumor model. Thereby, synergizing CDT with ICD-driven, in situ vaccine-like immunotherapy by immuno-nanozymes provides a novel and generalized paradigm for devising highly efficient and specific anti-tumor strategy without the use of external stimulations.

It is becoming more and more important to effectively integrate multiple complementary diagnostic imaging and synergistic therapies into a nano-platform, but it is still challenging. Here, we used bovine serum albumin (BSA) as a template to prepare ultra-small Ag/Gd2O3 (Ag/Gd@BSA) hybrid nanoparticles with high water dispersion by a biomineralization strategy for magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). Compared with commercial MR and CT contrast agents, we showed that these well-characterized BSA-templated nanotheranostics possessed higher r1 relaxivity (5.84 mM-1 s-1) and HU values. In addition, these nanotheranostics have an excellent NIR absorption feature and outstanding photothermal conversion efficiency (47.4%) in the solution phase. The in vivo imaging experiment demonstrated that the Ag/Gd@BSA hybrid nanoparticles could serve as tri-modality imaging contrast agents to enable precise diagnosis of tumors. Meanwhile, it was also revealed that Ag/Gd@BSA had ability to be an ideal nanotherapeutic agent to achieve a satisfactory tumor treatment effect through PTT. Also, we showed the good biocompatibility of Ag/Gd@BSA nanoparticles. Overall, these results indicated that Ag/Gd@BSA was an effective nanotheranostic, which could accurately identify tumor sites and realize complete tumor elimination, having great potential in clinical transformation.

采用浸泡-干燥和化学原位聚合的方法制备了聚吡咯/碳纳米管/棉纱(PPy/MWCNTs/CY)复合电极材料.探究了浸泡次数以及化学原位聚合掺杂剂浓度对电极电化学性能的影响.采用Phenom台式扫描电镜、冷场发射扫描电子显微镜、CHI660E电化学工作站和傅里叶红外光谱仪对电极的表观形貌、物质结构和组成进行了分析.研究结果表明:当MWCNTs浸泡次数为3次,对甲苯磺酸浓度为0.5 mol/L时,电极的比电容最大,为214 F/g(241.3 mF/cm),优于在棉纱上直接原位聚合聚吡咯的比电容.当恒电流充放电电流为3 mA时,PPy/MWCNTs/CY的放电时间大干PPy/CY的放电时间,此外PPy包覆的均匀性得到提高.

Sensitivity of magnetic resonance imaging (MRI) enhanced by T-1 or T-2 contrast agents remains an unmet medical need for accurate diagnosis of gliomas with infiltrative nature. Herein, we report the synthesis of bovine serum albumin-mediated KMnF3 nanocrystals (KMnF3@BSA NCs) via a simple "one-pot" biomimetic method. The KMnF3@BSA NCs composed of one paramagnetic component have high relaxivities (r(1) = 6.14 mM(-1).s(-1), r(2) = 149.69 mM(-1).s(-1)) and provide complementary T-1-T-2 dual-modal MRI images with the same in-plane geometries in glioma-bearing mice on a 7.0 T MRI scanner. Furthermore, algebra algorithm processing of the T-1 and T-2 images suppresses the ambiguity and greatly increases the contrast between tumors and the surrounding tissue, leading to an improved sensitivity. The biomimetic prepared KMnF3@BSA NCs thus have great potential in accurate MRI detection of gliomas. Moreover, this simple biomimetic method could be applied to prepare other complex metal fluorides.

Hypoxia within solid tumors severely limits the efficacy of photodynamic therapy (PDT). Biocompatible calcium peroxide nanoparticles (CaO2 NPs) have superior oxygen generating capacity for hypoxia relief but the relatively slow release of O2 from CaO2 NPs hampers the PDT efficacy enhancement. Herein, manganese dioxide (MnO2) is applied as a nanozyme to facilitate O2 release from CaO2 NPs. It is disclosed that the accelerated O2 release ensures a rapid and efficient amplification of the O2 level for an increased cytotoxic singlet oxygen production with chlorin e6 and leads to a down-regulated hypoxia-responsive protein expression, which eventually translates to a super-efficient PDT as evidenced by the complete eradication of mice bearing subcutaneous 4T1 tumors. Meanwhile, MnO2 imparts an MR T1 imaging modality for tumor detection and treatment planning. These findings signify the essential role of accelerated and efficient hypoxia relief in PDT efficacy enhancement and provide an effective paradigm to overcome hypoxia-associated resistance for an enhanced therapeutic efficacy.

Nanoscale photocatalysts have attracted abundant research attention in the solar-activated disinfection. In this work, we find that solar irradiation significantly improves the antimicrobial activity of graphene quantum dots (GQDs), accompanied by severe oxidative stress and membrane damage. By using electron spin resonance (ESR) technique, we confirm that different reactive oxygen species (ROS), including singlet oxygen (1O2), hydroxyl radical (•OH), and superoxide anion (O2•-) were generated by GQDs upon irradiation with simulated sunlight. Additionally, these generated ROS will further facilitate lipid peroxidation of cell membrane and suppress bacterial antioxidant systems, enhancing the phototoxicity of GQDs. These findings will bring major advancements of GQDs in applications of solar-driven bacterial disinfection.

Europium oxide nanoparticles are emerging as one of the most important oxide phosphors for a variety of applications. Currently, thermal decomposition is the most powerful approach to prepare europium oxide nanoparticles with narrow size and morphology distribution. However, an understanding of the relationship between thermal decomposition conditions on the corresponding photoluminescence (PL) performance of europium oxide nanoparticles remains unexplored so far. In this study, europium oxide nanoparticles were prepared through thermal decomposition under different conditions by controlling the concentration precursor or the solvent used for thermal decomposition and the PL properties of as-prepared europium oxide nanoparticles were investigated. The obtained PL spectra infer the coexistence of Eu3+ and Eu2+ emission centers in the as-prepared europium oxide nanoparticles. More importantly, it is evidenced that the control of the thermal decomposition conditions appears an effective way to modulate the relative fraction of Eu2+ and Eu3+ emission centers, which confers the PL emission of europium oxide nanoparticles from blue to red.