Colorimetric and Photothermal Dual-Modal Switching Lateral Flow Immunoassay Based on a Forced Dispersion Prussian Blue Nanocomposite for the Sensitive Detection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is a key marker for a prostate cancer diagnosis. The low sensitivity of traditional lateral flow immunoassay (LFIA) methods makes them unsuitable for point-of-care testing. Herein, we designed a nanozyme by in situ growth of Prussian blue (PB) within the pores of dendritic mesoporous silica (DMSN). The PB was forcibly dispersed into the pores of DMSN, leading to an increase in exposed active sites. Consequently, the atom utilization is enhanced, resulting in superior peroxidase (POD)-like activity compared to that of cubic PB. Antibody-modified DMSN@PB nanozymes serve as immunological probes in an enzymatic-enhanced colorimetric and photothermal dual-signal LFIA for PSA detection. After systematic optimization, the LFIA based on DMSN@PB successfully achieves a 4-fold amplification of the colorimetric signal within 7 min through catalytic oxidation of the chromogenic substrate by POD-like activity. Moreover, DMSN@PB exhibits an excellent photothermal conversion ability under 808 nm laser irradiation. Accordingly, photothermal signals are introduced to improve the anti-interference ability and sensitivity of LFIA, exhibiting a wide linear range (1-40 ng mL-1) and a low PSA detection limit (0.202 ng mL-1), which satisfies the early detection level of prostate cancer. This research provides a more accurate and reliable visualization analysis methodology for the early diagnosis of prostate cancer.

Stretchable Unsymmetrical Piezoelectric BiO2-x Deposited-Hydrogel as Multimodal Triboelectric Nanogenerators for Biomechanical Motion Harvesting.

Enhancing the output performance of triboelectric nanogenerators (TENGs) is essential for increasing their application in smart devices. Oxygen-vacancy-rich BiO2-x nanosheets (BiO2-x NSs) are advanced-engineered nanomaterials with excellent piezoelectric properties. Herein, a stretchable unsymmetrical BiO2-x NSs deposited-hydrogel made of polyacrylamide (PAM) as a multimodal TENG is rationally fabricated, and the performance of TENG can be tailored by controlling the BiO2-x NSs deposition amount and spatial distribution. The alteration of resistance caused by the Poisson effect of PAM/BiO2-x composite hydrogel (H-BiO2-x) can be used as a piezoresistive sensor, and the piezoelectricity of BiO2-x NSs can effectively enhance the density of transfer charge, thus improving the output performance of the H-BiO2-x-based TENG. In addition, the chemical cross-linking between the BiO2-x NSs and the PAM polymer chain allows the hydrogel electrode to have a higher tensile capacity (867%). Used for biomechanical motion signal detection, the sensors made of H-BiO2-x have high sensitivity (gauge factor = 6.93) and can discriminate a range of forces (0.1-5.0 N) at low frequencies (0.5-2.0 Hz). Finally, the prepared TENG can collect biological energy and convert it into electricity. Consequently, the improved TENG shows a good application prospect as multimodal biomechanical sensors by combining piezoresistive, piezoelectric, and triboelectric effects.

Revealing the Optimization Route of Piezoelectric Sonosensitizers: From Mechanism to Engineering Methods.

Piezoelectric catalysis is a novel catalytic technology that has developed rapidly in recent years and has attracted extensive interest among researchers in the field of tumor therapy for its acoustic-sensitizing properties. Nevertheless, researchers are still controversial about the key technical difficulties in the modulation of piezoelectric sonosensitizers for tumor therapy applications, which is undoubtedly a major obstacle to the performance modulation of piezoelectric sonosensitizers. Clarification of this challenge will be beneficial to the design and optimization of piezoelectric sonosensitizers in the future. Here, the authors start from the mechanism of piezoelectric catalysis and elaborate the mechanism and methods of defect engineering and phase engineering for the performance modulation of piezoelectric sonosensitizers based on the energy band theory. The combined therapeutic strategy of piezoelectric sonosensitizers with enzyme catalysis and immunotherapy is introduced. Finally, the challenges and prospects of piezoelectric sonosensitizers are highlighted. Hopefully, the explorations can guide researchers toward the optimization of piezoelectric sonosensitizers and can be applied in their own research.

A Vacancy-Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co-Activated Immunotherapy.

Low efficacy of immunotherapy due to the poor immunogenicity of most tumors and their insufficient infiltration by immune cells highlights the importance of inducing immunogenic cell death and activating immune system for achieving better treatment outcomes. Herein, ferroelectric Bi2CuO4 nanoparticles with rich copper vacancies (named BCO-VCu) are rationally designed and engineered for ferroelectricity-enhanced apoptosis, cuproptosis, and the subsequently evoked immunotherapy. In this structure, the suppressed recombination of the electron-hole pairs by the vacancies and the band bending by the ferroelectric polarization lead to high catalytic activity, triggering reactive oxygen species bursts and inducing apoptosis. The cell fragments produced by apoptosis serve as antigens to activate T cells. Moreover, due to the generated charge by the ferroelectric catalysis, this nanomedicine can act as "a smart switch" to open the cell membrane, promote nanomaterial endocytosis, and shut down the Cu+ outflow pathway to evoke cuproptosis, and thus a strong immune response is triggered by the reduced content of adenosine triphosphate. Ribonucleic acid transcription tests reveal the pathways related to immune response activation. Thus, this study firstly demonstrates a feasible strategy for enhancing the efficacy of immunotherapy using single ferroelectric semiconductor-induced apoptosis and cuproptosis.

Anti-Freezing and Ultrasensitive Zwitterionic Betaine Hydrogel-Based Strain Sensor for Motion Monitoring and Human-Machine Interaction.

Ultrasensitive and reliable conductive hydrogels are significant in the construction of human-machine twinning systems. However, in extremely cold environments, freezing severely limits the application of hydrogel-based sensors. Herein, building on biomimetics, a zwitterionic hydrogel was elaborated for human-machine interaction employing multichemical bonding synergies and experimental signal analyses. The covalent bonds, hydrogen bonds, and electrostatic interactions construct a dense double network structure favorable for stress dispersion and hydrogen bond regeneration. In particular, zwitterions and ionic conductors maintained excellent strain response (99 ms) and electrical sensitivity (gauge factor = 14.52) in the dense hydrogel structure while immobilizing water molecules to enhance the weather resistance (-68 °C). Inspired by the high sensitivity, zwitterionic hydrogel-based strain sensors and remote-control gloves were designed by analyzing the experimental signals, demonstrating promising potential applications within specialized flexible materials and human-machine symbiotic systems.

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

Synergizing Pyroelectric Catalysis and Enzyme Catalysis: Establishing a Reciprocal and Synergistic Model to Enhance Anti-Tumor Activity.

Nanozyme activity is greatly weakened by the microenvironment and multidrug resistance of tumor cells. Hence, a bi-catalytic nanoplatform, which promotes the anti-tumor activity through "charging empowerment" and "mutual complementation" processes involved in enzymatic and pyroelectric catalysis, by loading ultra-small nanoparticles (USNPs) of pyroelectric ZnSnO3 onto MXene nanozyme (V2 CTx nanosheets), is developed. Here, the V2 CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2 O2 to generate toxic ·OH, accelerated by the near-infrared (NIR) light mediated heat effect. The resulting V4+ is then converted to V3+ by oxidizing endogenous glutathione (GSH), realizing an enzyme-catalyzed cycle. However, the cycle will lose its persistence once GSH is insufficient; nevertheless, the pyroelectric charges generated by ZnSnO3 USNPs continuously support the V4+ /V3+ conversion and ensure nanoenzyme durability. Moreover, the hyperthermia arising from the V2 CTx nanosheets by NIR irradiation results in an ideal local temperature gradient for the ZnSnO3 USNPs, giving rise to an excellent pyroelectric catalytic effect by promoting band bending. Furthermore, polarized charges increase the tumor cell membrane permeability and facilitate nanodrug accumulation, thereby resolving the multidrug resistance issue. Thus, the combination of pyroelectric and enzyme catalysis together with the photothermal effect solves the dilemma of nanozymes and improves the antitumor efficiency.

Phase Engineered Cux S-Ag2 S with Photothermoelectric Activity for Enhanced Multienzyme Activity and Dynamic Therapy.

The insufficient exposure sites and active site competition of multienzyme are the two main factors to hinder its therapeutic effect. Here, a phase-junction nanomaterial (amorphous-crystalline Cux S-Ag2 S) is designed and prepared through a simple room temperature ion-exchange process. A small amount of Ag+ is added into Cu7 S4 nanocrystals, which transforms Cu7 S4 into amorphous phased Cux S and produces crystalline Ag2 S simultaneously. In this structure, the overhanging bonds on the amorphous Cux S surface provide abundant active sites for optimizing the therapeutic activity. Meanwhile, the amorphous state enhances the photothermal effect through non-radiative relaxation, and due to its low thermal resistance, phase-junction Cux S-Ag2 S forms a significant temperature gradient to unlock the optimized thermo-electrodynamic therapy. Furthermore, benefiting from the high asymmetry of the amorphous state, the material forms a spin-polarized state that can effectively inhibit electron-hole recombination. In this way, the thermoelectric effect can facilitate the enzyme-catalyzed cycle by providing electrons and holes, enabling an enhanced coupling of thermoelectric therapy with multienzyme activity, which induces excellent anti-tumor performance. More importantly, the catalytic process simulated by density-functional theory proves that Ag+ alleviates the burden on the Cu sites through favorable adsorption of O2 and prevents active site competition.

Architecture of Vanadium-Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy.

Taking the significance of the special microenvironment for tumor cell survival into account, disrupting tumor redox homeostasis is highly prospective for improving therapeutic efficacy. Herein, a multifunctional 2D vanadium-based MXene nanoplatform, V4 C3 /atovaquone@bovine albumin (V4 C3 /ATO@BSA, abbreviated as VAB) has been elaborately constructed for ATO-enhanced nanozyme catalytic/photothermal therapy. The redox homeostasis within the tumor cells is eventually disrupted, showing a remarkable anti-tumor effect. The VAB nanoplatform with mixed vanadium valence states can induce a cascade of catalyzed reactions in the tumor microenvironment, generating plenty of reactive oxygen species (ROS) with effective glutathione consumption to amplify oxidative stress. Meanwhile, the stable and strong photothermal effect of VAB under near-infrared irradiation not only causes the necrosis of tumor cells, but also improves its peroxidase-like activity. In addition, the release of ATO can effectively alleviate endogenous oxygen consumption to limit triphosadenine formation and inhibit mitochondrial respiration. As a result, the expression of heat shock proteins is effectively suppressed to overcome thermoresistance and the production of ROS can be further promoted due to mitochondrial injury. Moreover, VAB also presents high photoacoustic and photothermal imaging performances. In brief, the multifunctional nanoplatform can provide ATO-enhanced nanozyme catalytic/photothermal therapy with broadening the biomedical applications of vanadium-based MXene.

Structure Engineered High Piezo-Photoelectronic Performance for Boosted Sono-Photodynamic Therapy.

Sono-photodynamic therapy is hindered by the limited tissue penetration depth of the external light source and the quick recombination of electron-hole owing to the random movement of charge carriers. In this study, orthorhombic ZnSnO3 quantum dots (QDs) with piezo-photoelectronic effects are successfully encapsulated in hexagonal upconversion nanoparticles (UCNPs) using a one-pot thermal decomposition method to form an all-in-one watermelon-like structured sono-photosensitizer (ZnSnO3 @UCNPs). The excited near-infrared light has high penetration depth, and the watermelon-like structure allows for full contact between the UCNPs and ZnSnO3 QDs, achieving ultrahigh Förster resonance energy transfer efficiency of up to 80.30%. Upon ultrasonic and near-infrared laser co-activation, the high temperature and pressure generated lead to the deformation of the UCNPs, thereby driving the deformation of all ZnSnO3 QDs inside the UCNPs, forming many small internal electric fields similar to isotropic electric domains. This piezoelectric effect not only increases the internal electric field intensity of the entire material but also prevents random movement and rapid recombination of charge carriers, thereby achieving satisfactory piezocatalytic performance. By combining the photodynamic effect arising from the energy transfer from UCNPs to ZnSnO3 , synergistic efficacy is realized. This study proposes a novel strategy for designing highly efficient sono-photosensitizers through structural design.

A bubble-enhanced lanthanide-doped up/down-conversion platform with tumor microenvironment response for dual-modal photoacoustic and near-infrared-II fluorescence imaging.

As an important tumor diagnosis strategy in precision medicine, multimodal imaging has been widely studied. However, the weak imaging signal with low spatial resolution and the constant signal of lack of specific activation severely limit its disease diagnosis. Herein, a bubble-enhanced lanthanide-based up/down-conversion platform with tumor microenvironment response for dual-mode imaging, LDNP@DMSN-Au@CaCO3 nanoparticles (named as LDAC NPs) were successfully developed. Combining the advantages of photoacoustic imaging (PAI) and the second near-infrared window (NIR-II) fluorescence imaging (FI), significantly improved the accuracy of diseases diagnosis. LDAC NPs with flower-like structure were synthesized through the encapsulation of uniform lanthanide-doped nanoparticles (NaYbF4:Ce,Er@NaYF4 named LDNPs) with dendritic mesoporous silica (DMSN). The gold nanoparticles (Au NPs) were then in situ grown on the surface of DMSN and the surface were finally coated with a layer of calcium carbonate (CaCO3). Under the excitation of the 980 nm laser, LDNPs showed strong emission of NIR-II at 1550 nm due to the doping of Ce and Er ions, showcasing excellent spatial resolution and deep tissue penetration characteristics, while the resulting visible light emission (540 nm) enables Au NPs to generate PAI signals with the aid of LDNPs via the fluorescence resonance energy transfer effect. In acidic tumoral environment, CaCO3 layer could produce CO2 microbubbles, and the PAI signals of LDAC NPs could be further enhanced with the generation of CO2 bubbles due to the bubble cavitation effect. Simultaneously, the NIR-II FI of LDAC NPs was self-enhanced with the degradation of the CaCO3. This intelligent nanoparticle with stimulus-activated dual-mode imaging capability holds great promise in future precision diagnostics.

Mitochondria-targeting Cu3VS4 nanostructure with high copper ionic mobility for photothermoelectric therapy.

Thermoelectric therapy has emerged as a promising treatment strategy for oncology, but it is still limited by the low thermoelectric catalytic efficiency at human body temperature and the inevitable tumor thermotolerance. We present a photothermoelectric therapy (PTET) strategy based on triphenylphosphine-functionalized Cu3VS4 nanoparticles (CVS NPs) with high copper ionic mobility at room temperature. Under near-infrared laser irradiation, CVS NPs not only generate hyperthermia to ablate tumor cells but also catalytically yield superoxide radicals and induce endogenous NADH oxidation through the Seebeck effect. Notably, CVS NPs can accumulate inside mitochondria and deplete NADH, reducing ATP synthesis by competitively inhibiting the function of complex I, thereby down-regulating the expression of heat shock proteins to relieve tumor thermotolerance. Both in vitro and in vivo results show notable tumor suppression efficacy, indicating that the concept of integrating PTET and mitochondrial metabolism modulation is highly feasible and offers a translational promise for realizing precise and efficient cancer treatment.

Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes.

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007, nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity, low cost, mild reaction conditions, good stability, and suitable for large-scale production. Recently, with the cross fusion of nanomedicine and nanocatalysis, nanozyme-based theranostic strategies attract great attention, since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects. Thus, various nanozymes have been developed and used for tumor therapy. In this review, more than 270 research articles are discussed systematically to present progress in the past five years. First, the discovery and development of nanozymes are summarized. Second, classification and catalytic mechanism of nanozymes are discussed. Third, activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory, machine learning, biomimetic and chemical design. Then, synergistic theranostic strategy of nanozymes are introduced. Finally, current challenges and future prospects of nanozymes used for tumor theranostic are outlined, including selectivity, biosafety, repeatability and stability, in-depth catalytic mechanism, predicting and evaluating activities.

Design and Mechanism Insight of Monodispersed AuCuPt Alloy Nanozyme with Antitumor Activity.

The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes: glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multimetallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multimodal synergistic therapy. This study presents a typical paradigm to enable the use of multimetallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.

Multiple therapeutic mechanisms of pyrrolic N-rich g-C3N4 nanosheets with enzyme-like function in the tumor microenvironment.

Nanozyme-based synergistic catalytic therapies for tumors have attracted extensive research attention. However, the unsatisfactory efficiency and negative impact of the tumor microenvironment (TME) hinder its clinical applications. In this study, we provide an easy method to prepare transition metals loaded onto pyrrolic nitrogen-rich g-C3N4 (PN-g-C3N4) for forming metal-N4 sites. This N-rich material effectively transfers electrons from g-C3N4 to metal-N4 sites, promotes the oxidation-reduction reaction of metals with different valence states, and improves material reusability. Under TME conditions, copper ions loaded onto PN-g-C3N4 (Cu-PN-g-C3N4, CPC) can produce ·OH through a Fenton-like reaction for tumor inhibition. This Fenton-like reaction and tumor cell inhibition can be improved further by a photodynamic effect caused by light irradiation. We introduced upconversion nanoparticles (UCNPs) into CPC to obtain nano-enzymes (UCNPs@Cu-PN-g-C3N4, UCPC) for effectively penetrating the tissue, which emits light corresponding to the UV absorption region of CPC when excited with 980 nm near-infrared (NIR) light. The nanoplatform can reduce H2O2 concentration upon exposure to NIR light; this induces an increase in dissolved oxygen content and produces a higher supply of reactive oxygen species (ROS) for destroying tumor cells. Owing to the narrow bandgap (1.92 eV) of UCPC under 980 light irradiation, even under the condition of hypoxia, the excited electrons in the conduction band can reduce insoluble O2 through a single electron transfer process, thus effectively generating O2•-. Nanoenzyme materials with catalase properties produce three types of ROS (·OH, O2•- and 1O2) when realizing chemodynamic and photodynamic therapies. An excellent therapeutic effect was established by killing cells in vitro and the tumor-inhibiting effect in vivo, proving that the prepared nanoenzymes have an effective therapeutic effect and that the endogenous synergistic treatment of multiple treatment technologies can be realized.

Doping Engineering to Modulate Lattice and Electronic Structure for Enhanced Piezocatalytic Therapy and Ferroptosis.

Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to its deep tissue penetration depth and less O2 -dependence. However, the piezocatalytic therapeutic efficiency is limited owing to the poor piezoresponse, low separation of electron-hole pairs, and complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn-doped ZnO (Mn-ZnO) nanocluster with enhanced piezoelectric effect is constructed via doping engineering. Mn-doping not only induces lattice distortion to increase polarization but also creates rich oxygen vacancies (OV ) for suppressing the recombination of electron-hole pairs, leading to high-efficiency generation of ROS under ultrasound irradiation. Moreover, Mn-doped ZnO shows TME-responsive multienzyme-mimicking activity and glutathione (GSH) depletion ability owing to the mixed valence of Mn (II/III), further aggravating oxidative stress. Density functional theory calculations show that Mn-doping can improve the piezocatalytic performance and enzyme activity of Mn-ZnO due to the presence of OV . Benefiting from the boosting of ROS generation and GSH depletion ability, Mn-ZnO can significantly accelerate the accumulation of lipid peroxide and inactivate glutathione peroxidase 4 (GPX4) to induce ferroptosis. The work may provide new guidance for exploring novel piezoelectric sonosensitizers for tumor therapy.

Sm/Co-Doped Silica-Based Nanozymes Reprogram Tumor Microenvironment for ATP-Inhibited Tumor Therapy.

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co-doped mesoporous silica with 3PO-loaded nanozymes (denoted as mSC-3PO) are rationally constructed for simultaneously inhibiting energy production by adenosine triphosphate (ATP) inhibitor 3PO and reprogramming TME by multiactivities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase-like, catalase-like activity, and glutathione peroxidase-like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over-expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC-3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co-doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double-center catalytic process (Sm3+ and Co3+ /Co2+ ). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near-infrared (NIR) light absorption of mSC-3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation-promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance.

Uncovering Different Responses and Energy Mechanisms of Sensitizer and Activator in Host Manipulation for Upconversion Nanoparticles.

Agile and efficient upconversion luminescence (UCL) fine-tuning strategies are the most demanded for in the frontier applications of highly doped upconversion nanoparticles (UCNPs). By doping Zn2+ ions into NaHoF4 and NaGdF4:Yb3+ shells using the oleate method, the separate influences of Zn2+ on Ho3+ and Yb3+ ions in UCL-related processes were analyzed in detail, revealing relevant UCL changes and underlying energy mechanisms from a novel but explicit perspective. Different behaviors of green and red UCL before and after Zn2+-ion doping were attributed to the disparities in the energy pathways and features of the sample structures. Herein, the populations of 5S2/5F4 and 5F5 states, not the usually mentioned decay time, decided the UCL intensities of the NaHoF4@NaYbF4-structured highly doped UCNPs. The advantageous small sizes and intense single-band red UCL of these UCNPs were further developed by combining our previous strategies with introducing Zn2+ ions into the NaHoF4 matrix. Overcoming energy loss by surface quenchers and Zn2+-triggered inner defects is the key factor in maximizing 4f-4f transitions. To the best of our knowledge, the current study is the first attempt to date to experimentally reveal separate impacts of the heteroions on activators and sensitizers in UCL-related processes and can deepen the theoretical investigation of Ho-based UCL for the broadened applications of NaHoF4 UCNPs.

2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy.

Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO4 artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy-rich BiVO4 nanosheets (abbreviated Vv -r BiVO4 NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the Vv -r BiVO4 NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O2 /O2 •- and H2 O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, Vv -r BiVO4 NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.

Dual-inhibition of lactate metabolism and Prussian blue-mediated radical generation for enhanced chemodynamic therapy and antimetastatic effect.

Numerous research studies have proved that lactate is pivotal in tumor proliferation, metastasis, and recurrence, so disrupting the lactate metabolism in the tumor microenvironment (TME) has become one of the effective methods of tumor treatment. Herein, we have developed a versatile nanoparticle (HCLP NP) based on hollow Prussian blue (HPB) as the functional carrier for loading α-cyano-4-hydroxycinnamate (CHC), and lactate oxidase (LOD), followed by coating with polyethylene glycol to enhance chemodynamic therapy (CDT) and the antimetastatic effect of cancer. The obtained HCLP NPs would be degraded under endogenous mild acidity within the TME to simultaneously release CHC and LOD. CHC inhibits the expression of monocarboxylate transporter 1 in tumors, thereby interrupting the uptake of lactate from the outside and alleviating tumor hypoxia by reducing lactate aerobic respiration. Meanwhile, the released LOD can catalyze the decomposition of lactate into hydrogen peroxide, further enhancing the efficacy of CDT by generating plenty of toxic reactive oxygen species through the Fenton reaction. The strong absorbance at about 800 nm endows HCLP NPs with excellent photoacoustic imaging properties. Both in vitro and in vivo studies have demonstrated that HCLP NPs can inhibit tumor growth and metastasis, providing a new possibility for tumor therapy.