An Ultrasmall SnFe2O4 Nanozyme with Endogenous Oxygen Generation and Glutathione Depletion for Synergistic Cancer Therapy

The tumor microenvironment (TME) with the characteristics of severe hypoxia, overexpressed glutathione (GSH), and high levels of hydrogen peroxide (H₂O₂) dramatically limits the antitumor efficiency by monotherapy. Herein, a novel TME-modulated nanozyme employing tin ferrite (SnFe₂O₄, abbreviated as SFO) is presented for simultaneous photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The as-fabricated SFO nanozyme demonstrates both catalase-like and GSH peroxidase-like activities. In the TME, the activation of H₂O₂ leads to the generation of hydroxyl radicals (•OH) in situ for CDT and the consumption of GSH to relieve antioxidant capability of the tumors. Meanwhile, the nanozyme can catalyze H₂O₂ to generate oxygen to meliorate the tumor hypoxia, which is beneficial to achieve better PDT. Furthermore, the SFO nanozyme irradiated with 808 nm laser displays a prominent phototherapeutic effect on account of the enhanced photothermal conversion efficiency (η  = 42.3%) and highly toxic free radical production performance. This “all in one” nanozyme integrated with multiple treatment modalities, computed tomography, and magnetic resonance imaging properties, and persistent modulation of TME exhibits excellent tumor theranostic performance. This strategy may provide a new dimension for the design of other TME-based anticancer strategies.     

Tumor Microenvironment‐Responsive Mesoporous MnO2‐Coated Upconversion Nanoplatform for Self‐Enhanced Tumor Theranostics

The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO₂) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME‐enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO₂) with covalently loaded chlorin e6 are obtained as near‐infrared light mediated PDT agents, and then a mMnO₂ shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO₂ degrades rapidly within the TME, releasing Mn²⁺ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a self‐enhanced imaging. Significantly, the degradation of mMnO₂ shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H₂O₂ and reduction of glutathione, thus achieving a highly potent chemo‐photodynamic therapy.     

Persistent Regulation of Tumor Microenvironment via Circulating Catalysis of MnFe2O4@Metal–Organic Frameworks for Enhanced Photodynamic Therapy

Reactive oxygen species (ROS)‐based cancer therapy, such as photodynamic therapy (PDT), is subject to the hypoxia and overexpressed glutathione (GSH) found in the tumor microenvironment (TME). Herein, a novel strategy is reported to continuously and simultaneously regulate tumor hypoxia and reducibility in order to achieve the desired therapeutic effect. To accomplish this, a biocompatible nanoplatform (MnFe₂O₄@metal–organic framework (MOF)) is developed by integrating a coating of porphyrin‐based MOF as the photosensitizer and manganese ferrite nanoparticle (MnFe₂O₄) as the nanoenzyme. The synthetic MnFe₂O₄@MOF nanoplatform exhibits both catalase‐like and glutathione peroxidase‐like activities. Once internalized in the tumor, the nanoplatform can continuously catalyze H₂O₂ to produce O₂ to overcome the tumor hypoxia by cyclic Fenton reaction. Meanwhile, combined with the Fenton reaction, MnFe₂O₄@MOF is able to persistently consume GSH in the presence of H₂O₂, which decreases the depletion of ROS upon laser irradiation during PDT and achieves better therapeutic efficacy in vitro and in vivo. Moreover, the nanoplatform integrates a treatment modality with magnetic resonance imaging, along with persistent regulation of TME, to promote more precise and effective treatment for future clinical application.     

Biodegradable Fe(III)@WS2‐PVP Nanocapsules for Redox Reaction and TME‐Enhanced Nanocatalytic,Photothermal, and Chemotherapy

In this study, biocompatible Fe(III) species‐WS₂‐polyvinylpyrrolidone (Fe(III) @ WS₂‐PVP) nanocapsules with enhanced biodegradability and doxorubicin (DOX) loading capacity are one‐pot synthesized. In this nanocapsule, there exists a redox reaction between Fe(III) species and WS₂ to form Fe²⁺ and WO₄^2?. The formed Fe²⁺ could be oxidized to Fe³⁺, which reacts with Fe(III) @ WS₂‐PVP again to continuously produce Fe²⁺ and WO₄^2?. Such a repeated endogenous redox reaction leads to an enhanced biodegradation and DOX release of DOX @ Fe(III) @ WS₂‐PVP. More strikingly, the Fe²⁺ generation and DOX release are further accelerated by the overexpressed H₂O₂ and the mild acidic tumor microenvironment (TME), since H₂O₂ and H⁺ can accelerate the oxidation of Fe²⁺. The continuously generated Fe²⁺ catalyzes a fast Fenton reaction with the innate H₂O₂ in tumor cells and produces abundant highly toxic hydroxyl radicals for nanocatalytic tumor therapy. Together with the high photothermal transforming capability, the DOX @ Fe(III) @WS₂‐PVP nanocapsules successfully achieve the endogenous redox reaction and exogenous TME‐augmented tumor photothermal therapy, chemo and nanocatalytic therapy outcome. The concept of material design can be innovatively extended to the synthesis of biodegradable Fe(III) @ MoS₂‐PVP nanocomposite, thus paving a promising novel way for the rational design of intelligent theranostic agents for highly efficient treatment of cancer.     

Smart Tumor Microenvironment‐Responsive Nanotheranostic Agent for Effective Cancer Therapy

The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO₂‐loaded, bovine serum albumin, and PEG co‐modified mesoporous CaSiO₃ nanoparticles (CaM‐PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO₂ NPs generate O₂ in situ by reacting with endogenous H₂O₂, relieving the hypoxic state of the TME that further modulates the cancer cell cycle status to S phase, which improves the potency of co‐loaded S phase‐sensitive chemotherapeutic drugs. After the hypoxia relief, CaM‐PB can sustainably release drugs due to the enlarged pores of mesoporous CaSiO₃ in the acidic TME, preventing the drug pre‐leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn²⁺ released from the MnO₂ NPs at tumor sites can potentially serve as a diagnostic agent, enabling the identification of tumor regions by T₁‐weighted magnetic resonance imaging during therapy. In vivo pharmacodynamics results demonstrate that these synergetic effects caused by CaM‐PB NPs significantly contribute to the inhibition of tumor progression. Therefore, the CaM‐PB NPs with sequential theranostic functions are a promising system for effective cancer therapy.     

Self-Reliant Nanomedicine with Long-Lasting Glutathione Depletion Ability Disrupts Adaptive Redox Homeostasis and Suppresses Cancer Stem Cells

Bulk cancer cells and cancer stem cells (CSCs) harbor efficient and adaptive redox systems to help them resist oxidative insults arising from diverse therapeutic modalities. Herein, a tumor microenvironment (TME)-activatable nano-modulator capable of disrupting adaptive redox homeostasis, prepared by integrating FDA-approved xCT inhibitor sulfasalazine (SSZ) into pH-responsive hydroxyethyl starch-doxorubicin conjugate stabilized copper peroxide nanoparticles (HSCPs) is reported. Compared to poly(vinylpyrrolidone) (PVP)-stabilized copper peroxide nanoparticles, HSCPs exhibit superior physiological stability, longer circulation half-life, and higher tumor enrichment. Under an acidic TME, the active components inside HSCPs are productively released along with the disintegration of HSCPs. The specifically generated hydrogen peroxide (H₂O₂) from copper peroxide nanoparticles furnishes a constant power source for copper-mediated hydroxyl radical (•OH) production, serving as a wealthy supplier for oxidative stress. Meanwhile, the tumor-specific release of Cu²⁺ and SSZ can induce long-lasting glutathione (GSH) depletion via copper-mediated self-cycling valence transitions and SSZ-blocked GSH biosynthesis, thereby reducing the offsetting action of the antioxidant GSH against oxidative stress. As a result, this sustained oxidative stress potently restrains the growth of aggressive orthotopic breast tumors while suppressing pulmonary metastasis by eradicating CSC populations. The reported smart nanomedicine provides a new paradigm for redox imbalance-triggered cancer therapy.     

Thermochemotherapy Meets Tissue Engineering for Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is an autoimmune disease that progresses from inflammation to cartilage destruction. Inspired by the similar characteristics of inflammatory granulation tissue to those of tumors, the newly emerged tumor therapy called thermochemotherapy is proposed to treat RA. Meanwhile, the repair of cartilage injury via tissue engineering is paid attention simultaneously. A first-line antirheumatic drug (MTX; methotrexate) and transforming growth factor β1 (TGF-β1) are loaded in nano-Fe₃O₄ composite chitosan-polyolefin to construct a multifunctional hydrogel (DN-Fe-MTX-TGFβ1). The mechanical properties of the hydrogel are equivalent to that of articular cartilage to guarantee its role as a scaffold. A long-term release ability and the magnetocaloric properties of the hydrogel assure its effect to provide sustained local thermochemotherapy. The effective ability of the hydrogel for both anti-inflammation and cartilage repair is demonstrated. This work indicates a promising way to combine thermochemotherapy and tissue engineering for the effective treatment of RA for the first time.     

Tumor Microenvironment-Responsive Nanocarrier Based on VOx Nanozyme Amplify Oxidative Stress for Tumor Therapy

The construction of a novel nanocarrier that can break the redox balance in tumor cell is a promising anti-tumor strategy. Herein, a tumor microenvironment (TME)-responsive nanocarrier VC@Lipo is rationally designed by embedding ultrasmall VO_x nanozyme and photosensitizer chlorin e6 (Ce6) into liposomes. The size of VC@Lipo nanocarrier is ≈35 nm and can be degraded in the weakly acidic environment of TME. The VO_x nanozyme exhibits peroxidase-like activity and generates highly toxic hydroxyl radical ∙OH through Fenton-like reaction and ¹O₂ in the presence of H₂O₂ independent of light, and more ¹O₂ can be generated by the photodynamic effect of Ce6. In addition, the VO_x nanozyme can effectively deplete intracellular overexpressed glutathione (GSH) through redox reactions. In vivo experiments demonstrate that the nanocarrier shows excellent biocompatibility, presents the largest enrichment at the tumor site after 6 h of intravenous injection into mice with the highest tumor inhibition rate of 54.18% after laser irradiation. Compared with the single treatment mode, VC@Lipo shows the best synergistic effect of chemodynamic-photodynamic therapy. This work provides a new paradigm for nanocatalytic therapy of cancer and is expected to provide new ideas for precision medicine in cancer.     

Design of Hybrid MnO2‐Polymer‐Lipid Nanoparticles with Tunable Oxygen Generation Rates and Tumor Accumulation for Cancer Treatment

Manganese dioxide (MnO₂) nanoparticles (NPs) were discovered in previous work to be effective in improving tumor oxygenation (hypoxia) and reducing H₂O₂ and acidity in the tumor microenvironment (TME) via local injection. To develop MnO₂ formulations useful for clinical application, hybrid NPs are designed with tailored hydrophobicity and structure suitable for intravenous injection, with good blood circulation, biocompatibility, high tumor accumulation, and programmable oxygen generation rate. Two different hybrid NPs are constructed by embedding polyelectrolyte‐MnO₂ (PMD) in hydrophilic terpolymer/protein‐MnO₂ (TMD) or hydrophobic polymer/lipid‐MnO₂ (LMD) matrices. The in vitro reactivity of the MnO₂ toward H₂O₂ is controlled by matrix material and NP structure and dependent on pH with up to two‐fold higher O₂ generation rate at acidic (tumor) pH than at systemic pH. The hybrid NPs are found to be safe to cells in vitro and organs in vivo and effectively decrease tumor hypoxia and hypoxia‐inducible‐factor‐1alpha through local or systemic administration. Fast acting TMD reduces tumor hypoxia by 70% in 0.5 h by local injection. Slow acting LMD exhibits superior tumor accumulation and retention through the systemic administration and decreased hypoxia by 45%. These findings encourage a broader use of hybrid MD NPs to overcome TME factors for cancer treatment.     

Recent Advances in Nanomaterial-Based Nanoplatforms for Chemodynamic Cancer Therapy

Triggered by the endogenous chemical energy in the tumor microenvironment (TME), chemodynamic therapy (CDT) as an emerging non-exogenous stimulant therapeutic modality has received increasing attention in recent years. The chemodynamic agents can convert internal hydrogen peroxide (H₂O₂) into the lethal reactive oxygen species (ROS) hydroxyl radicals (^•OH) for oncotherapy. Compared with other therapeutic modalities, CDT possesses many notable advantages, such as tumor-specific, highly selective, fewer systemic side effects, and no need for external stimulation. Nevertheless, mild acid pH, low H₂O₂ content, and overexpressed reducing substance in TME severely suppressed the CDT efficiency. With the rapid development of nanotechnology, some kinds of nanomaterials have been utilized with improved CDT efficiency. In particular, the excellent photo-, ultrasound-, magnetic-, and other stimuli-response properties of nanomaterials make it possible for combination cancer therapy of CDT with other therapeutic modalities, and it has shown superior anti-cancer activity than monotherapies. Therefore, it is necessary to summarize the application of nanomaterial-based chemodynamic cancer therapy. In this review, the various nanomaterials-based nanoplatforms for CDT and its combinational therapies are summarized and discussed, aiming to provide inspiration for the design of better-quality agents to promote the CDT development and lay the foundation for its future conversion to clinical applications.     

Biodegradable Calcium Phosphate Nanotheranostics with Tumor-Specific Activatable Cascade Catalytic Reactions-Augmented Photodynamic Therapy

Photodynamic therapy (PDT) is exploited as a promising strategy for cancer treatment. However, the hypoxic solid tumor and the lack of tumor-specific photosensitizer administration hinder the further application of oxygen (O₂)-dependent PDT. In this study, a biodegradable and O₂ self-supplying nanoplatform for tumor microenvironment (TME)-specific activatable cascade catalytic reactions-augmented PDT is reported. The nanoplatform (named GMCD) is constructed by coloading catalase (CAT) and sinoporphyrin sodium (DVDMS) in the manganese (Mn)-doped calcium phosphate mineralized glucose oxidase (GOx) nanoparticles. The GMCD can effectively accumulate in tumor sites to achieve an “off to on” fluorescence transduction and a TME-activatable magnetic resonance imaging. After internalization into cancer cells, the endogenous hydrogen peroxide (H₂O₂) can be catalyzed to generate O₂ by CAT, which not only promotes GOx catalytic reaction to consume more intratumoral glucose, but also alleviates tumor hypoxia and enhances the production of cytotoxic singlet oxygen from light-triggered DVDMS. Moreover, the H₂O₂ generated by GOx-catalysis can be converted into highly toxic hydroxyl radicals by Mn²⁺-mediated Fenton-like reaction, further amplifying the oxidative damage of cancer cells. As a result, GMCD displays superior therapeutic effects on 4T1-tumor bearing mice by a long term cascade catalytic reactions augmented PDT.     

Copper(I) Phosphide Nanocrystals for In Situ Self‐Generation Magnetic Resonance Imaging‐Guided Photothermal‐Enhanced Chemodynamic Synergetic Therapy Resisting Deep‐Seated Tumor

Fe‐based Fenton agents can generate highly reactive and toxic hydroxyl radicals (·OH) in the tumor microenvironment (TME) for chemodynamic therapy (CDT) with high specificity. However, the strict condition (lower pH environment: 3–4) of the highly efficient Fenton reaction limits its practical application in the clinic. Development of new CDT agents more suitable for TME is significant and challenging. A highly efficient Cu(I)‐based CDT agent, copper(I) phosphide nanocrystals (CP NCs), which is more adaptable to the pH value of TME than Fe‐based agents, thereby producing more ·OH to trigger the apoptosis of cancer cells, is prepared. Moreover, the excess glutathione (GSH) in TME can reduce the Cu(II) produced by a Fenton‐like reaction to Cu(I), further increasing the generation rate of ·OH and relieving tumor antioxidant ability. Furthermore, owing to their strong absorption in the NIR II region, CP NCs exhibit an excellent photothermal conversion effect, which can further improve the Fenton reaction. What is more, CP NCs can act as in situ self‐generation magnetic resonance imaging (MRI) agents owing to the generation of paramagnetic Cu(II) in response to excess H₂O₂ in the TME. These properties may open up the exploration of copper‐based materials in clinical application of self‐generation imaging‐guided synergetic treatment.     

Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair

Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound-modulatable hydrogel platform with selenoprotein-mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen-enriched selene-incorporated thin-shell silicon within methacrylate gelatin (O₂-PSSG). The resultant construct orchestrates the modulation of the bone-defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium-containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O₂-PSSG rapidly releases selenocystine ([Sec]₂) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β-catenin pathways and promotes the differentiation of BMSCs. Consequently, O₂-PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US-responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration.     

Injectable Adhesive Hydrogel as Photothermal-Derived Antigen Reservoir for Enhanced Anti-Tumor Immunity

Low vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ-forming MnO₂ nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO₂ nanoparticles induces immunogenic cell death to release mass autologous tumor-derived protein antigens under near-infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ-forming adhesive hydrogel. The antigens-captured adhesive hydrogel acts as an “antigen reservoir” and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti-tumor immune response mediated by CD8⁺ T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel-based photothermal therapy. Therefore, the proposed “antigen reservoir” strategy shows the great potential application as an in situ-forming personalized vaccine to enhancing the cancer immune therapy.     

Quantitative Photoacoustic Diagnosis and Precise Treatment of Inflammation In Vivo Using Activatable Theranostic Nanoprobe

Excessive production of reactive oxygen species such as H₂O₂ is the pathological basis of chronic inflammatory diseases, as well as bacterial infection‐induced inflammation. Therefore, the in situ H₂O₂ level is a reliable biomarker of inflammatory responses, and its real‐time measurement can monitor disease progression and improve therapeutic outcomes in inflammation‐linked diseases. However, the currently used strategies for the diagnosis of inflammation is mainly through routine blood test, which are limited in determining the inflammation status and cannot provide comprehensive quantitative information. In this work, a novel H₂O₂‐responsive theranostic nanoplatform comprising Ag shell coated Pd‐tipped gold nanorods (Au–Pd@Ag NR) is developed. The etching and oxidation of the Ag shell by H₂O₂ release the Ag ions, which effectively kill bacteria in vivo and trigger their absorption variation at 700 and 1260 nm. The ratiometric photoacoustic (PA) imaging at 1260 and 700 nm (PA₁₂₆₀/PA₇₀₀) accurately quantifies H₂O₂ in a mice model of bacterial infection and abdomen inflammation, even in a rabbit model of osteoarthritis. The H₂O₂ activated second near‐infrared (NIR‐II) PA images of the probe can further precisely differentiate the inflammation region and normal tissue. This nanoplatform not only can quantify H₂O₂ during inflammation but also act as a potent antibacterial agent.     

Chitosan Hydrogel‐Capped Porous SiO2 as a pH Responsive Nano‐Valve for Triggered Release of Insulin

A pH responsive, chitosan‐based hydrogel film is used to cap the pores of a porous SiO₂ layer. The porous SiO₂ layer is prepared by thermal oxidation of an electrochemically etched Si wafer, and the hydrogel film is prepared by reaction of chitosan with glycidoxypropyltrimethoxysilane (GPTMS). Optical reflectivity spectroscopy and scanning electron microscopy (SEM) confirm that the bio‐polymer only partially infiltrates the porous SiO₂ film, generating a double layer structure. The optical reflectivity spectrum displays Fabry–Pérot interference fringes characteristic of a double layer, which is characterized using reflective interferometric Fourier transform spectroscopy (RIFTS). Monitoring the position of the RIFTS peak corresponding to the hydrogel layer allows direct, real‐time observation of the reversible volume phase transition of the hydrogel upon cycling of pH in the range 6.0–7.4. The swelling ratio and response time are controlled by the relative amount of GPTMS in the hydrogel. The pH‐dependent volume phase transition can be used to release insulin trapped in the porous SiO₂ layer underneath the hydrogel film. At pH 7.4, the gel in the top layer effectively blocks insulin release, while at pH 6.0 insulin penetrates the swollen hydrogel layer, resulting in a steady release into solution.     

Uniform Rattle‐type Hollow Magnetic Mesoporous Spheres as Drug Delivery Carriers and their Sustained‐Release Property

A novel kind of rattle‐type hollow magnetic mesoporous sphere (HMMS) with Fe₃O₄ particles encapsulated in the cores of mesoporous silica microspheres has been successfully fabricated by sol–gel reactions on hematite particles followed by cavity generation with hydrothermal treatment and H₂ reduction. Such a structure has the merits of both enhanced drug‐loading capacity and a significant magnetization strength. The prepared HMMSs realize a relatively high storage capacity up to 302 mg g^?1 when ibuprofen is used as a model drug, and the IBU–HMMS system has a sustained‐release property, which follows a Fick's law.     

Protein‐Release Behavior of Self‐Assembled PEG–β‐Cyclodextrin/PEG–Cholesterol Hydrogels

This paper reports on the degradation and protein release behavior of a self‐assembled hydrogel system composed of β‐cyclodextrin‐ (βCD) and cholesterol‐derivatized 8‐arm star‐shaped poly(ethylene glycol) (PEG₈). By mixing βCD‐ and cholesterol‐derivatized PEG₈ (molecular weights 10, 20 and 40 kDa) in aqueous solution, hydrogels with different rheological properties are formed. It is shown that hydrogel degradation is mainly the result of surface erosion, which depends on the network swelling stresses and initial crosslink density of the gels. This degradation mechanism, which is hardly observed for other water‐absorbing polymer networks, leads to a quantitative and nearly zero‐order release of entrapped proteins. This system therefore offers great potential for protein delivery.     

Ultra-Steep-Slope and High-Stability of CuInP2S6/WS2 Ferroelectric Negative Capacitor Transistors by Passivation Effect and Dual-Gate Modulation

Ferroelectric negative capacitance transistors (Fe-NCFETs) have emerged as a promising technology for low-power electronics and have the potential to continue Moore's law. However, the existing 2D ferroelectric materials are predominantly sulfides or halides, which are susceptible to oxidation or hydrolysis, thereby hindering their commercial production due to concerns related to performance and stability. To address these obstacles, the authors have optimized the Fe-NCFETs composed of 2D ferroelectric CuInP₂S₆ and semiconductor WS₂ using high-k Al₂O₃ passivation and dual-gate modulation strategy. With atomic layer deposition (ALD) of Al₂O₃, all-2D Fe-NCFETs, operated at a low driven voltage of 0.3 V, achieve much improvement in stability and performance with a high ON/OFF ratio of 10⁹ and minimum subthreshold swing (SS) of 14 mV dec⁻¹, which is attributed to the negative capacitance effect of CuInP₂S₆ and passivation effect of ALD-Al₂O₃. The dual-gate modulation approach is also implemented to maintain the device stability and enable the improved ON/OFF ratio from 10⁵ to 10⁸, minimum SS of 10 mV dec⁻¹, and an average SS of ≈60 mV dec⁻¹ covering more than five orders of magnitude of current. This work provides a facile and effective strategy for designing all-2D Fe-NCFETs with ultra-steep SS and high stability, showing exciting potential for future low-power electronic applications.     

MnO2 Gatekeeper: An Intelligent and O2‐Evolving Shell for Preventing Premature Release of High Cargo Payload Core,Overcoming Tumor Hypoxia,and Acidic H2O2‐Sensitive MRI

Premature leakage of photosensitizer (PS) from nanocarriers significantly reduces the accumulation of PS within a tumor, thereby enhancing nonspecific accumulation in normal tissues, which inevitably leads to a limited efficacy for photodynamic therapy (PDT) and the enhanced systematic phototoxicity. Moreover, local hypoxia of the tumor tissue also seriously hinders the PDT. To overcome these limitations, an acidic H₂O₂‐responsive and O₂‐evolving core–shell PDT nanoplatform is developed by using MnO₂ shell as a switchable shield to prevent the premature release of loaded PS in core and elevate the O₂ concentration within tumor tissue. The inner core SiO₂‐methylene blue obtained by co‐condensation has a high PS payload and the outer MnO₂ shell shields PS from leaking into blood after intravenous injection until reaching tumor tissue. Moreover, the shell MnO₂ simultaneously endows the theranostic nanocomposite with redox activity toward H₂O₂ in the acidic microenvironment of tumor tissue to generate O₂ and thus overcomes the hypoxia of cancer cells. More importantly, the Mn(ΙΙ) ion reduced from Mn(ΙV) is capable of in vivo magnetic resonance imaging selectively in response to overexpressed acidic H₂O₂. The facile incorporation of the switchable MnO₂ shell into one multifunctional diagnostic and therapeutic nanoplatform has great potential for future clinical application.