Tumor Metabolism‐Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron–Hole Pairs’ Separation

Reactive oxygen species (ROS) depletion and low ROS production that result from the intratumoral redox metabolism equilibrium and low energy conversion efficiency from ultrasound mechanical energy to ROS‐represented chemical energy, respectively, are two vital inhibitory factors of sonodynamic therapy (SDT). To address the two concerns, a tumor metabolism‐engineered composite nanoplatform capable of intervening intratumoral ROS metabolism, breaking the redox equilibrium, and reshaping the tumor microenvironment is constructed to reinforce SDT against tumors. In this metabolism‐engineered nanoplatform, Nb₂C nanosheets serve as the scaffold to accommodate TiO₂ sonosensitizers and l ‐buthionine‐sulfoximine. Systematic experiments show that such nanoplatforms can reduce ROS depletion via suppressing glutathione synthesis and simultaneously improving ROS production via the Nb₂C‐enhanced production and separation of electron–hole pairs. Contributed by the combined effect, net ROS content can be significantly elevated, which results in the highly efficient anti‐tumor outcomes in vivo and in vitro. Moreover, the combined design principles, that is, tumor metabolism modulation for reducing ROS depletion and electron–hole pair separation for facilitating ROS production, can be extended to other ROS‐dependent therapeutic systems.     

Piezoelectric‐Effect‐Enhanced Full‐Spectrum Photoelectrocatalysis in p–n Heterojunction

Photoelectrochemical (PEC) water splitting offers a promising strategy for converting solar energy to chemical fuels. Herein, a piezoelectric‐effect–enhanced full‐spectrum photoelectrocatalysis with multilayered coaxial titanium dioxide/barium titanate/silver oxide (TiO₂/BTO/Ag₂O) nanorod array as the photoanode is reported. The vertically grown nanorods ensure good electron conductivity, which enables fast transport of the photogenerated electrons. Significantly, the insertion of a piezoelectric BaTiO₃ (BTO) nanolayer at the p‐type Ag₂O and n‐type TiO₂ interface created a polar charge‐stabilized electrical field. It maintains a sustainable driving force that attract the holes of TiO₂ and the electrons of Ag₂O, resulting in greatly increased separation and inhibited recombination of the photogenerated carriers. Furthermore, Ag₂O as a narrow bandgap semiconductor has a high ultraviolet–visible–near infrared (UV–vis–NIR) photoelectrocatalytic activity. The TiO₂/BTO/Ag₂O, after poling, successfully achieves a prominent photocurrent density, as high as 1.8 mA cm^?2 at 0.8 V versus Ag/Cl, which is about 2.6 times the TiO₂ nanorod photoanode. It is the first time that piezoelectric BaTiO₃ is used for tuning the interface of p‐type and n‐type photoelectrocatalyst. With the enhanced light harvesting, efficient photogenerated electron–hole pairs' separation, and rapid charge transfer at the photoanode, an excellent photoelectrocatalytic activity is realized.     

A Novel Approach for Achieving High‐Efficiency Photoelectrochemical Water Oxidation in InGaN Nanorods Grown on Si System: MXene Nanosheets as Multifunctional Interfacial Modifier

MXene nanosheets with attractive electrical conductivity and tunable work function have been adopted as multifunctional interfacial modifier between InGaN nanorods and Si for photoelectrochemical water oxidation for the first time. Compared to bare InGaN/Si systems, MXene interfacial layers give rise to an ultralow onset potential of 75 mV versus reversible hydrogen electrode (RHE), which is the highest ever reported for InGaN‐ or Si‐based photoanodes by interfacial modification. Furthermore, the modified photoanode exhibits a significantly enhanced photocurrent density (7.27 mA cm^?2) at 1.23 V versus RHE, which is about 10 times higher than that achieved with the InGaN/Si photoanode. The detailed mechanism demonstrates that the formed type‐II band alignment in InGaN/MXene heterojunction and an Ohmic junction at the MXene/Si interface make MXene an ideal electron‐migration channel to enhance charge separation and transfer process. This synergetic effect of MXene can significantly decrease the charge resistance at semiconductor/Si and semiconductor/electrolyte hetero‐interfaces, eventually resulting in the fast hole injection efficiency of 82% and superior stability against photocorrosion. This work not only provides valuable guidance for designing high‐efficiency photoelectrodes through the integration of multiscale and multifunctional materials, but also presents a novel strategy for achieving high‐performance artificial photosynthesis by introducing interfacial modifier.     

An O2 Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H2O/H2O2 Splitting for Tumor Imaging and Photodynamic Therapy

Conventional photodynamic therapy (PDT) has limited applications in clinical cancer therapy due to the insufficient O₂ supply, inefficient reactive oxygen species (ROS) generation, and low penetration depth of light. In this work, a multifunctional nanoplatform, upconversion nanoparticles (UCNPs)@TiO₂@MnO₂ core/shell/sheet nanocomposites (UTMs), is designed and constructed to overcome these drawbacks by generating O₂ in situ, amplifying the content of singlet oxygen (¹O₂) and hydroxyl radical (?OH) via water‐splitting, and utilizing 980 nm near‐infrared (NIR) light to increase penetration depth. Once UTMs are accumulated at tumor site, intracellular H₂O₂ is catalyzed by MnO₂ nanosheets to generate O₂ for improving oxygen‐dependent PDT. Simultaneously, with the decomposition of MnO₂ nanosheets and 980 nm NIR irradiation, UCNPs can efficiently convert NIR to ultraviolet light to activate TiO₂ and generate toxic ROS for deep tumor therapy. In addition, UCNPs and decomposed Mn²⁺ can be used for further upconversion luminescence and magnetic resonance imaging in tumor site. Both in vitro and in vivo experiments demonstrate that this nanoplatform can significantly improve PDT efficiency with tumor imaging capability, which will find great potential in the fight against tumor.     

Flexible MXene Framework as a Fast Electron/Potassium-Ion Dual-Function Conductor Boosting Stable Potassium Storage in Graphite Electrodes

Graphite anodes show great potential for potassium storage, however, their capacity fades quickly owing to substantial interlayer expansion/shrinkage (i.e., up to 60%) induced structural degradation. Here, Ti₃C₂T_x MXene nanosheets are used as a fast electron/potassium-ion dual-function conductor to construct the framework of all-integrated graphite nanoflake (GNF)/MXene (GNFM) electrodes. The continuous MXene framework constructs a 3D channel for fast electron/potassium-ion transfer and endows GNFM electrodes with a high structural stability. Owing to this unique MXene framework, GNFM electrodes exhibit much enhanced potassium storage performances than that of the conventional polymer-bonded electrodes even at high mass loadings. Moreover, GNFM electrodes also show impressive cyclability in non-flammable electrolytes and are further used as anodes to assemble novel non-flammable potassium-ion capacitors that show an excellent cyclability and high energy/power densities (113.1 Wh kg^–1 and 12.2 kW kg^–1). New insights into phase transition mechanism in GNFM electrodes are verified by operando XRD. Density functional theory calculations demonstrate that MXene can promote electron transfer and potassium diffusion in the heterointerface between GNF and MXene. Therefore, the results demonstrate that all-integrated GNFM electrodes designed with MXene as multifunctional frameworks provide a new paradigm for producing efficient potassium storage anodes.     

2D MXene Nanofilms with Tunable Gas Transport Channels

2D materials' membranes with well‐defined nanochannels are promising for precise molecular separation. Herein, the design and engineering of atomically thin 2D MXene flacks into nanofilms with a thickness of 20 nm for gas separation are reported. Well‐stacked pristine MXene nanofilms are proven to show outstanding molecular sieving property for H₂ preferential transport. Chemical tuning of the MXene nanochannels is also rationally designed for selective permeating CO₂. Borate and polyethylenimine (PEI) molecules are well interlocked into MXene layers, realizing the delicate regulation of stacking behaviors and interlayer spacing of MXene nanosheets. The MXene nanofilms with either H₂‐ or CO₂‐selective transport channels exhibit excellent gas separation performance beyond the limits for state‐of‐the‐art membranes. The mechanisms within these nanoconfined MXene layers are discussed, revealing the transformation from “diffusion‐controlled” to “solution‐controlled” channels after chemical tuning. This work of precisely tailoring the 2D nanostructure may inspire the exploring of nanofluidics in 2D confined space with applications in many other fields like catalysis and energy conversion processes.     

Layered Orthorhombic Nb2O5@Nb4C3Tx and TiO2@Ti3C2Tx Hierarchical Composites for High Performance Li‐ion Batteries

Engineering electrode nanostructures is critical in developing high‐capacity, fast rate‐response, and safe Li‐ion batteries. This study demonstrates the synthesis of orthorhombic Nb₂O₅@Nb₄C₃T_x (or @Nb₂CT_x) hierarchical composites via a one‐step oxidation —in flowing CO₂ at 850 °C —of 2D Nb₄C₃T_x (or Nb₂CT_x) MXene. The composites possess a layered architecture with orthorhombic Nb₂O₅ nanoparticles decorated uniformly on the surface of the MXene flakes and interconnected by disordered carbon. The composites have a capacity of 208 mAh g^?1 at a rate of 50 mA g^?1 (0.25 C) in 1–3 V versus Li⁺/Li, and retain 94% of the specific capacity with 100% Coulombic efficiency after 400 cycles. The good electrochemical performances could be attributed to three synergistic effects: (1) the high conductivity of the interior, unoxidized Nb₄C₃T_x layers, (2) the fast rate response and high capacity of the external Nb₂O₅ nanoparticles, and (3) the electron “bridge” effects of the disordered carbon. This oxidation method was successfully extended to Ti₃C₂T_x and Nb₂CT_x MXenes to prepare corresponding composites with similar hierarchical structures. Since this is an early report on producing this structure, there is much room to push the boundaries further and achieve better electrochemical performance.     

Reactive Oxygen Species–Activatable Liposomes Regulating Hypoxic Tumor Microenvironment for Synergistic Photo/Chemodynamic Therapies

Tumors have adapted various cellular antidotes and microenvironmental conditions to subsist against photodynamic therapy (PDT) and chemodynamic therapy (CDT). Here, the development of reactive oxygen species (ROS)‐activatable liposomes (RALP) for therapeutic enhancement by simultaneously addressing the critical questions in PDT and CDT is reported. The design of RALP@HOC@Fe₃O₄ features ROS‐cleavable linker molecules for improved tumor penetration/uptake and ondemand cargo releasing, and integration of Fe₃O₄ and an oxaliplatin prodrug for smart regulation of hypoxia tumor microenvironment. Glutathione stored by the tumor cells is consumed by the prodrug to produce highly toxic oxaliplatin. Depletion of glutathione not only avoids the undesired annihilation of ROS in PDT, but also modulates the chemical specie equilibria in tumors for H₂O₂ promotion, leading to greatly relieved tumor hypoxia and PDT enhancement. Synergistically, Fe (II) in the hybrid RALP formulation can be fuelled by H₂O₂ to generate ?OH in the Fenton reaction, thus elevating CDT efficiency. This work offers a strategy for harnessing smart, responsive, and biocompatible liposomes to enhance PDT and CDT by regulating tumor microenvironment, highlighting a potential clinical translation beneficial to patients with cancer.     

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.     

MXene‐Bonded Flexible Hard Carbon Film as Anode for Stable Na/K‐Ion Storage

Hard carbon (HC) is a promising anode material for sodium‐ion batteries (SIBs) and potassium‐ion batteries (PIBs), but the volume change during the insertion/extraction of Na⁺ or K⁺ limits the cycle life, especially for PIBs due to the large ion size of K⁺. Moreover, the conventional anodes fabricated through the coating method cannot satisfy the requirement of flexible devices. Here, it is shown that 2D carbide flakes of Ti₃C₂T_x MXene can be used as multifunctional conductive binders for flexible HC electrodes. The use of MXene nanosheets eliminates the need for all the electrochemically inactive components in the conventional polyvinylidene fluoride–bonded HC electrode, including polymer binders, conductive additives, and current collectors. In MXene‐bonded HC electrodes, conductive and hydrophilic MXene 2D nanosheets construct a 3D network, which can effectively stabilize the electrode structure and accommodate the volume expansion of HC during the charge/discharge process, leading to an enhanced electrode capacity and excellent cycle performance as anodes for both SIBs and PIBs. Benefiting from the 3D conductive network, the MXene‐bonded HC film electrodes also present improved rate capability, indicating MXene is a very promising multifunctional binder for next‐generation flexible secondary rechargeable batteries.     

Electrostatic Self‐Assembly of Nanosized Carbon Nitride Nanosheet onto a Zirconium Metal–Organic Framework for Enhanced Photocatalytic CO2 Reduction

UiO‐66, a zirconium based metal–organic framework, is incorporated with nanosized carbon nitride nanosheets via a facile electrostatic self‐assembly method. This hybrid structure exhibits a large surface area and strong CO₂ capture ability due to the introduction of UiO‐66. We demonstrate that electrons from the photoexcited carbon nitride nanosheet can transfer to UiO‐66, which can substantially suppress electron–hole pair recombination in the carbon nitride nanosheet, as well as supply long‐lived electrons for the reduction of CO₂ molecules that are adsorbed in UiO‐66. As a result, the UiO‐66/carbon nitride nanosheet heterogeneous photocatalyst exhibits a much higher photocatalytic activity for the CO₂ conversion than that of bare carbon nitride nanosheets. We believe this self‐assembly method can be extended to other carbon nitride nanosheet loaded materials.     

Three Birds,One‐Stone Strategy for Hybrid Microwave Synthesis of Ta and Sn Codoped Fe2O3@FeTaO4 Nanorods for Photo‐Electrochemical Water Oxidation

A “three birds, one stone” strategy is proposed to enhance the performance of hematite photoanode for photoelectrochemical water splitting. One‐pot hybrid microwave synthesis of Ta and Sn codoped Fe₂O₃@FeTaO₄ core–shell nanorods on F:SnO₂ substrate achieves three synergetic effects simultaneously: i) core–shell heterojunction formation to alleviate the significant electron–hole recombination; ii) preserved morphology of small‐diameter nanorods to provide a short hole diffusion distance; and iii) Ta and Sn codoping to enhance the electrical conductivity. These effects are not possible with conventional high temperature thermal synthesis in a furnace. As a result, core–shell Fe₂O₃@FeTaO₄ electrode with FeOOH cocatalyst achieves a photocurrent density of 2.86 mA cm^?2 at 1.23 V_RHE under AM 1.5 G simulated sunlight (100 mW cm^?2), which is ≈2.4 times higher than that of bare hematite (1.17 mA cm^?2). In addition, the FeOOH/Fe₂O₃@FeTaO₄ electrode exhibits a high surface charge separation efficiency of ≈85% and a modest bulk charge separation efficiency of ≈24%.     

A Self-Assembled Vertical-Gradient and Well-Dispersed MXene Structure for Flexible Large-Area Perovskite Modules

Advancing hole transport layers (HTL) to realize large-area, flexible, and high-performance perovskite solar cells (PSCs) is one of the most challenging issues for its commercialization. Here, a self-assembled gradient Ti₃C₂T_x MXene incorporated PEDOT:PSS HTL is demonstrated to achieve high-performance large-area PSCs by establishing half-caramelization-based glucose-induced MXene redistribution. Through this process, the Ti₃C₂T_x MXene nanosheets are spontaneously dispersed and redistributed at the top region of HTL to form the unique gradient distribution structure composed of MXene:Glucose:PEDOT:PSS (MG-PEDOT). These results show that the MG-PEDOT HTL not only offers favorable energy level alignment and efficient charge extraction, but also improves the film quality of perovskite layer featuring enlarged grain size, lower trap density, and longer carrier lifetime. Consequently, the power conversion efficiency (PCE) of the flexible device based on MG-PEDOT HTL is increased by 36% compared to that of pristine PEDOT:PSS HTL. Meanwhile, the flexible perovskite solar minimodule (15 cm² area) using MG-PEDOT HTL achieve a PCE of 17.06%. The encapsulated modules show remarkable long-term storage stability at 85 °C in ambient air (≈90% efficiency retention after 1200 h) and enhanced operational lifetime (≈90% efficiency retention after 200 h). This new approach shows a promising future of the self-assembled HTLs for developing optoelectronic devices.     

Flexible Carbon Dots-Intercalated MXene Film Electrode with Outstanding Volumetric Performance for Supercapacitors

2D MXenes have emerged as promising supercapacitor electrode materials due to their metallic conductivity, pseudo-capacitive mechanism, and high density. However, layer-restacking is a bottleneck that restrains their ionic kinetics and active site exposure. Herein, a carbon dots-intercalated strategy is proposed to fabricate flexible MXene film electrodes with both large ion-accessible active surfaces and high density through gelation of calcium alginate (CA) within the MXene nanosheets followed by carbonization. The formation of CA hydrogel within the MXene nanosheets accompanied by evaporative drying endow the MXene/CA film with high density. In the carbonization process, the CA-derived carbon dots can intercalate into the MXene nanosheets, increasing the interlayer spacing and promoting the electrolytic diffusion inside the MXene film. Consequently, the carbon dots-intercalated MXene films exhibit high volumetric capacitance (1244.6 F cm⁻³ at 1 A g⁻¹), superior rate capability (662.5 F cm⁻³ at 1000 A g⁻¹), and excellent cycling stability (93.5% capacitance retention after 30 000 cycles) in 3 m H₂SO₄. Additionally, an all-solid-state symmetric supercapacitor based on the carbon dots-intercalated MXene film achieves a high volumetric energy density of 27.2 Wh L⁻¹. This study provides a simple yet efficient strategy to construct high-volumetric performance MXene film electrodes for advanced supercapacitors.     

Platinum-based photosensitizer with near-infrared aggregation-induced emission for synergistic photodynamic-chemo theranostics

Photodynamic therapy (PDT) is of great interest as an emerging paradigm towards cancer treatment, owing to its advantages of minimal invasiveness and low toxicity. In this work, we incorporated cisplatin into an AIE-based photosensitizer (BT) and achieved a highly efficient antitumor drug (BT-Pt). Possessing AIE characteristics, BT-Pt exhibited NIR fluorescence with large Stokes shift in cells, which can guide the location of the drug. More importantly, the ROS generation efficiency of BT-Pt has extremely been promoted with the fabrication of cisplatin, compared with BT. As a result, BT-Pt demonstrated favorable therapeutic efficacy with a half maximal inhibitory concentration (IC₅₀) value of 1.54 μM for HeLa cells upon white light irradiation, attributed to its synergetic PDT and chemotherapy. The design strategy of such platinated photosensitizer showed great potential in developing multifunctional anticancer drugs with combinatorial photodynamic–chemotherapy, especially when ablating cisplatin resistant cancer cells and hypoxic tumors.     

Electronic Modulation of Metal–Organic Frameworks by Interfacial Bridging for Efficient pH-Universal Hydrogen Evolution

Designing well-defined interfacial chemical bond bridges is an effective strategy to optimize the catalytic activity of metal–organic frameworks (MOFs), but it remains challenging. Herein, a facile in situ growth strategy is reported for the synthesis of tightly connected 2D/2D heterostructures by coupling MXene with CoBDC nanosheets. The multifunctional MXene nanosheets with high conductivity and ideal hydrophilicity as bridging carriers can ensure structural stability and sufficient exposure to active sites. Moreover, the Co–O–Ti bond bridging formed at the interface effectively triggers the charge transfer and modulates the electronic structure of the Co-active site, which enhances the reaction kinetics. As a result, the optimized CoBDC/MXene exhibits superior hydrogen evolution reaction (HER) activity with low overpotentials of 29, 41, and 76 mV at 10 mA cm⁻² in alkaline, acidic, and neutral electrolytes, respectively, which is comparable to commercial Pt/C. Theoretical calculation demonstrates that the interfacial bridging-induced electron redistribution optimizes the free energy of water dissociation and hydrogen adsorption, resulting in improved hydrogen evolution. This study not only provides a novel electrocatalyst for efficient HER at all pH conditions but also opens up a new avenue for designing highly active catalytic systems.     

Strain Sensors with a High Sensitivity and a Wide Sensing Range Based on a Ti3C2Tx (MXene) Nanoparticle–Nanosheet Hybrid Network

A high sensitivity and large stretchability are desirable for strain sensors in wearable applications. However, these two performance indicators are contradictory, since the former requires a conspicuous structural change under a tiny strain, whereas the latter demands morphological integrity upon a large deformation. Developing strain sensors with both a high sensitivity (gauge factor (GF) > 100) and a broad strain range (>50%) is a considerable challenge. Herein, a unique Ti₃C₂T_x MXene nanoparticle–nanosheet hybrid network is constructed. The migration of nanoparticles leads to a large resistance variation while the wrapping of nanosheet bridges the detached nanoparticles to maintain the connectivity of the conductive pathways in a large strain region. The synergetic motion of nanoparticles and nanosheets endows the hybrid network with splendid electrical–mechanical performance, which is reflected in its high sensitivity (GF > 178.4) over the entire broad range (53%), the super low detection limit (0.025%), and a good cycling durability (over 5000 cycles). Such high performance endows the strain sensor with the capability for full‐range human motion detection.     

Does Excess Energy Assist Photogeneration in an Organic Low‐Bandgap Solar Cell?

The field dependence of the photocurrent in a bilayer assembly is measured with the aim to clarify the role of excess photon energy in an organic solar cell comprising a polymeric donor and an acceptor. Upon optical excitation of the donor an electron is transferred to the acceptor forming a Coulomb‐bound electron–hole pair. Since the subsequent escape is a field assisted process it follows that photogeneration saturates at higher electric fields, the saturation field being a measure of the separation of the electron–hole pair. Using the low bandgap polymers, PCDTBT and PCPDTBT, as donors and C₆₀ as acceptor in a bilayer assembly it is found that the saturation field decreases when the photon energy is roughly 0.5 eV above the S₁–S₀ 0–0 transition of the donor. This translates into an increase of the size of the electron‐hole‐pair up to about 13 nm which is close to the Coulomb capture radius. This increase correlates with the onset of higher electronic states that have a highly delocalized character, as confirmed by quantum‐chemical calculations. This demonstrates that accessing higher electronic states does favor photogeneration yet excess vibrational energy plays no role. Experiments on intrinsic photogeneration in donor photodiodes without acceptors support this reasoning.     

In Situ Polymerized Hollow Mesoporous Organosilica Biocatalysis Nanoreactor for Enhancing ROS‐Mediated Anticancer Therapy

The combination of reactive oxygen species (ROS)‐involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhancing ROS‐mediated cancer treatment. Herein, an in situ polymerized hollow mesoporous organosilica nanoparticle (HMON) biocatalysis nanoreactor is reported to integrate the synergistic effect of PDT/CDT for enhancing ROS‐mediated pancreatic ductal adenocarcinoma treatment. 2‐(1‐hexyloxyethyl)‐2‐devinylpyropheophorbide‐a photosensitizer is hybridized within the framework of HMON via an “in situ framework growth” approach. Then, the hollow cavity of HMONs is exploited as a nanoreactor for “in situ polymerization” to synthesize the polymer containing thiol groups, thereby enabling the immobilization of ultrasmall gold nanoparticles, which behave like glucose oxidase‐like nanozyme, converting glucose into H₂O₂ to provide self‐supplied H₂O₂ for CDT. Meanwhile, Cu²⁺‐tannic acid complexes are further deposited on the surface of HMONs (HMON‐Au@Cu‐TA) to initiate Fenton‐like reaction to covert the self‐supplied H₂O₂ into ?OH, a highly toxic ROS. Finally, collagenase (Col), which can degrade the collagen I fiber in the extracellular matrix, is loaded into HMON‐Au@Cu‐TA to enhance the penetration of HMONs and O₂ infiltration for enhanced PDT. This study provides a good paradigm for enhancing ROS‐mediated antitumor efficacy. Meanwhile, this research offers a new method to broaden the application of silica based nanotheranostics.     

Tumor-Activated Prodrug with Synergistic Anti-Stemness Chemical and Photodynamic Therapies

Photodynamic therapy (PDT) has received extensive attention as a promising cancer treatment approach. Still, challenges to in vivo photodynamic therapy have existed for decades. First, the “always on” nature of conventional photosensitizers will cause damage to normal tissues thereby limiting the treatment efficiency of PDT. Second, the hypoxic TME protects cancer stem cells (CSCs) deeply harbored in the center of tumors from PDT administration, thus contributing to the recrudescence and metastasis of tumors. Herein, a ROS-triggered self-immolative therapeutic prodrug ( Mu-PS ) is reported, comprising of an activatable photosensitizer, an indomethacin (IMC) part, and a ROS-responsive trigger, for the anti-stemness chemical and photodynamic therapy of tumors. Intriguingly, Mu-PS can target the tumor and selectively release the photosensitizer and IMC upon the activation of TME-related ROS, generating massive phototoxic ¹O₂ to kill most non-CSCs tumor cells under the action of PDT and block the growth of CSCs by IMC, hence, it multiplies the therapeutic index. Noteworthy, the anti-stemness mechanism of IMC in tumors is confirmed and elucidated for the first time. Overall, this study introduces a self-immolatative prodrug for combined CSCs-involved chemical therapy and activatable PDT for tumors and provides a design paradigm of prodrug for the precise prognosis and treatment of tumors.