A Multifunctional Cascade Bioreactor Based on Hollow‐Structured Cu2MoS4 for Synergetic Cancer Chemo‐Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu₂MoS₄ (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo‐dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu^1+/2+, Mo^4+/6+) exhibit Fenton‐like, glutathione (GSH) peroxidase‐like and catalase‐like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton‐like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase‐like CMS could react with endogenous H₂O₂ to generate O₂ for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H₂O₂. The regenerated H₂O₂ can devote to Fenton‐like reaction for realizing GOx‐catalysis‐enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor‐killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O₂^?) generation performance. More importantly, the PEGylated CMS@GOx‐based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.     

Nanocatalysts‐Augmented and Photothermal‐Enhanced Tumor‐Specific Sequential Nanocatalytic Therapy in Both NIR‐I and NIR‐II Biowindows

The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor‐specific therapy, here a novel concept of photothermal‐enhanced sequential nanocatalytic therapy in both NIR‐I and NIR‐II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (?OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H₂O₂ by glucose oxidase (GOD), an Fe₃O₄/GOD‐functionalized polypyrrole (PPy)‐based composite nanocatalyst is constructed to achieve diagnostic imaging‐guided, photothermal‐enhanced, and TME‐specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H₂O₂ level, and the integrated Fe₃O₄ component then catalyzes H₂O₂ into highly toxic ?OH to efficiently induce cancer‐cell death. Importantly, the high photothermal‐conversion efficiency (66.4% in NIR‐II biowindow) of the PPy component elevates the local tumor temperature in both NIR‐I and NIR‐II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H₂O₂ for enhancing the nanocatalytic‐therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.     

A Glucose/Oxygen‐Exhausting Nanoreactor for Starvation‐ and Hypoxia‐Activated Sustainable and Cascade Chemo‐Chemodynamic Therapy

Fenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H₂O₂ to highly toxic HO?. However, problems such as insufficient H₂O₂ levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe³⁺) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe³⁺–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H₂O₂ production and TA‐accelerated Fe³⁺/Fe²⁺ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO? for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.     

Wet/Sono‐Chemical Synthesis of Enzymatic Two‐Dimensional MnO2 Nanosheets for Synergistic Catalysis‐Enhanced Phototheranostics

2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug‐loading capacity, and excellent photothermal conversion. However, few studies report their “enzyme‐like” catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one‐step wet‐chemical method is first proposed for protein‐directed synthesis of 2D MnO₂ nanosheets (M‐NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono‐chemical approach is introduced for surface functionalization of the M‐NSs with high dispersity/stability as well as metal‐cation‐chelating capacity, which can not only chelate ⁶⁴Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn²⁺ for enhanced biosafety. Interestingly, the resulting M‐NS exhibits excellent enzyme‐like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well‐designed M‐NS can achieve effective photoacoustic‐imaging‐guided synergistic starvation‐enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small‐sized and ultrathin M‐NSs, which will broaden the application of 2D nanomaterials.     

H2S‐Scavenged and Activated Iron Oxide‐Hydroxide Nanospindles for MRI‐Guided Photothermal Therapy and Ferroptosis in Colon Cancer

Overproduced hydrogen sulfide (H₂S) is of vital importance for the progress of colon cancer and promotes cancer cellular proliferation. Devising pharmacological nanomaterials for tumor‐specific H₂S activation will be significant for precise colon cancer treatment. Herein, a biocompatible fusiform iron oxide‐hydroxide nanospindles (FeOOH NSs) nanosystem for magnetic resonance imaging (MRI), ferroptosis, and H₂S based cascade reaction‐enhanced combinational colon cancer treatment is developed. The FeOOH NSs can effectively scavenge endogenous H₂S via the reduction reaction to prohibit the growth of CT26 colon cancer. The cascade produced FeS driven by overexpressed H₂S exhibits near‐infrared‐triggered photothermal therapy capability and Fe²⁺‐mediated ferroptosis functionality. Meanwhile, the as‐prepared FeOOH NSs can light up tumor tissues as a potent MRI contrast agent. Additionally, FeOOH NSs present desirable biosafety in a murine model for up to three months and avoid any long‐term toxicity. Furthermore, it is found that these H₂S‐responsible nanotheranostics do not cause any cure effects on other cancer types, such as 4T1 breast cancer. Overall, the findings illustrate that the biocompatible FeOOH NSs can be successfully employed as a theranostic for specifically treating colon cancer, which may promote the clinical translation and development of H₂S‐responsive nanoplatforms.     

Polyaniline Nanovesicles for Photoacoustic Imaging‐Guided Photothermal‐Chemo Synergistic Therapy in the Second Near‐Infrared Window

Photoacoustic imaging‐guided photothermal therapy in the second near‐infrared (NIR‐II) window shows promise for clinical deep‐penetrating tumor phototheranostics. However, ideal photothermal agents in the NIR‐II window are still rare. Here, the emeraldine salt of polyaniline (PANI‐ES), especially synthesized by a one‐pot enzymatic reaction on sodium bis(2‐ethylhexyl) sulfosuccinate (AOT) vesicle surface (PANI‐ES@AOT, λ_max ≈ 1000 nm), exhibits excellent dispersion in physiological environment and remarkable photothermal ability at pH 6.5 (photothermal conversion efficiency of 43.9%). As a consequence of the enhanced permeability and retention effect of tumors and the doping‐induced photothermal effect of PANI‐ES@AOT, this pH‐sensitive NIR‐II photothermal agent allows tumor acidity phototheranostics with minimized pseudosignal readout and subdued normal tissue damage. Moreover, the enhanced fluidity of vesicle membrane triggered by heating is beneficial for drug release and allows precise synergistic therapy for an improved therapeutic effect. This study highlights the potential of template‐oriented (or interface‐confined) enzymatic polymerization reactions for the construction of conjugated polymers with desired biomedical applications.     

Recent Advances in Glucose‐Oxidase‐Based Nanocomposites for Tumor Therapy

Glucose oxidase (GOx) can react with intracellular glucose and oxygen (O₂) to produce hydrogen peroxide (H₂O₂) and gluconic acid, which can cut off the nutrition source of cancer cells and consequently inhibit their proliferation. Therefore, GOx is recognised as an ideal endogenous oxido‐reductase for cancer starvation therapy. This process can further regulate the tumor microenvironment by increasing the hypoxia and the acidity. Thus, GOx offers new possibilities for the elaborate design of multifunctional nanocomposites for tumor therapy. However, natural GOx is expensive to prepare and purify and exhibits immunogenicity, short in vivo half‐life, and systemic toxicity. Furthermore, GOx is highly prone to degrade after exposure to biological conditions. These intrinsic shortcomings will undoubtedly limit its biomedical applications. Accordingly, some nanocarriers can be used to protect GOx from the surrounding environment, thus controlling or preserving the activity. A variety of nanocarriers including hollow mesoporous silica nanoparticles, metal–organic frameworks, organic polymers, and magnetic nanoparticles are summarized for the construction of GOx‐based nanocomposites for multimodal synergistic cancer therapy. In addition, current challenges and promising developments in this area are highlighted.     

A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy

Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) are prepared through a novel top‐down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR‐light‐to‐heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug‐loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top‐down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging‐guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.     

Dual‐Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second Near‐Infrared Window Photothermal Therapy: A Comparative Study

Near‐infrared (NIR) light is widely used for noninvasive optical diagnosis and phototherapy. However, current research focuses on the first NIR window (NIR‐I, 650–950 nm), while the second NIR window (NIR‐II, 1000–1700 nm) is far less exploited. The development of the first organic photothermal nanoagent (SPN_I‐II) with dual‐peak absorption in both NIR windows and its utilization in photothermal therapy (PTT) are reported herein. Such a nanoagent comprises a semiconducting copolymer with two distinct segments that respectively and identically absorb NIR light at 808 and 1064 nm. With the photothermal conversion efficiency of 43.4% at 1064 nm generally higher than other inorganic nanomaterials, SPN_I‐II enables superior deep‐tissue heating at 1064 nm over that at 808 nm at their respective safety limits. Model deep‐tissue cancer PTT at a tissue depth of 5 mm validates the enhanced antitumor effect of SPN_I‐II when shifting laser irradiation from the NIR‐I to the NIR‐II window. The good biodistribution and facile synthesis of SPN_I‐II also allow it to be doped with an NIR dye for fluorescence‐imaging‐guided NIR‐II PTT through systemic administration. Thus, this study paves the way for the development of new polymeric nanomaterials to advance phototherapy.     

Rational Design of Multifunctional Fe@γ‐Fe2O3@H‐TiO2 Nanocomposites with Enhanced Magnetic and Photoconversion Effects for Wide Applications: From Photocatalysis to Imaging‐Guided Photothermal Cancer Therapy

Titanium dioxide (TiO₂) has been widely investigated and used in many areas due to its high refractive index and ultraviolet light absorption, but the lack of absorption in the visible–near infrared (Vis–NIR) region limits its application. Herein, multifunctional Fe@γ‐Fe₂O₃@H‐TiO₂ nanocomposites (NCs) with multilayer‐structure are synthesized by one‐step hydrogen reduction, which show remarkably improved magnetic and photoconversion effects as a promising generalists for photocatalysis, bioimaging, and photothermal therapy (PTT). Hydrogenation is used to turn white TiO₂ in to hydrogenated TiO₂ (H‐TiO₂), thus improving the absorption in the Vis–NIR region. Based on the excellent solar‐driven photocatalytic activities of the H‐TiO₂ shell, the Fe@γ‐Fe₂O₃ magnetic core is introduced to make it convenient for separating and recovering the catalytic agents. More importantly, Fe@γ‐Fe₂O₃@H‐TiO₂ NCs show enhanced photothermal conversion efficiency due to more circuit loops for electron transitions between H‐TiO₂ and γ‐Fe₂O₃, and the electronic structures of Fe@γ‐Fe₂O₃@H‐TiO₂ NCs are calculated using the Vienna ab initio simulation package based on the density functional theory to account for the results. The reported core–shell NCs can serve as an NIR‐responsive photothermal agent for magnetic‐targeted photothermal therapy and as a multimodal imaging probe for cancer including infrared photothermal imaging, magnetic resonance imaging, and photoacoustic imaging.     

Generalized Synthesis of Ultrathin Cobalt‐Based Nanosheets from Metallophthalocyanine‐Modulated Self‐Assemblies for Complementary Water Electrolysis

The development of effective approaches for preparing large‐area, self‐standing, ultrathin metal‐based nanosheets, which have proved to be favorable for catalytic applications such as water electrolysis, is highly desirable but remains a great challenge. Reported herein is a simple and versatile strategy to synthesize ultrathin Co₃O₄ and CoP NSs consisting of close‐packed nanoparticles by pyrolyzing cobalt(II) phthalocyanine/graphene oxide (CoPc/GO) assemblies in air and subsequent topotactic phosphidation while preserving the graphene‐like morphology. The strong π–π stacking interactions between CoPc and GO, and the inhibiting effect of the tetrapyrrole‐derived macrocycle for grain growth during the catalytic carbon gasification contribute to the NSs forming. The resulting homologous Co₃O₄ and CoP NSs display outstanding catalytic activity in alkaline media toward the oxygen evolution reaction and the hydrogen evolution reaction, respectively, ascribed to the richly exposed active sites, and the expedited electrolyte/ion transmission path. The integrated asymmetrical two‐electrode configuration also presents a superior cell voltage of 1.63 V at 10 mA cm^?2 for overall water splitting, accompanied with the excellent durability during long‐term cycling. Further evidences validate that this strategy is appropriate to fabricate graphene‐like ultrathin NSs of many other metal oxides, such as Fe₂O₃, NiO, MoO₃, and mixed‐metal oxides, for various applications.     

A Cascade Nanoreactor of Metal-Protein-Polyphenol Capsule for Oxygen-Mediated Synergistic Tumor Starvation and Chemodynamic Therapy

Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)-mediated glycolysis is oxygen-dependent, the cascade reaction based on GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H₂O₂ into O₂, starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close-loop strategy for on demand H₂O₂ and O₂ delivery, release, and recycling is proposed. The nanoreactor (metal-protein-polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O₂ consumption and the produced H₂O₂ reacts with Hb to produce highly cytotoxic hydroxyl radicals (•OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen-mediated synergistic starvation therapy and chemodynamic therapy.     

Co‐Based Catalysts Derived from Layered‐Double‐Hydroxide Nanosheets for the Photothermal Production of Light Olefins

Solar‐driven Fischer–Tropsch synthesis represents an alternative and potentially low‐cost route for the direct production of light olefins from syngas (CO and H₂). Herein, a series of novel Co‐based photothermal catalysts with different chemical compositions are successfully fabricated by H₂ reduction of ZnCoAl‐layered double‐hydroxide nanosheets at 300–700 °C. Under UV–vis irradiation, the photothermal catalyst prepared at 450 °C demonstrates remarkable CO hydrogenation performance, affording an olefin (C_2–4⁼) selectivity of 36.0% and an olefin/paraffin ratio of 6.1 at a CO conversion of 15.4%. Characterization studies using X‐ray absorption fine structure and high‐resolution transmission electron microscopy reveal that the active catalyst comprises Co and Co₃O₄ nanoparticles on a ZnO–Al₂O₃ mixed metal oxide support. Density functional theory calculations further demonstrate that the oxide‐decorated metallic Co nanoparticle heterostructure weakens the further hydrogenation ability of the corresponding Co, leading to the high selectivity to light olefins. This study demonstrates a novel solar‐driven catalyst platform for the production of light olefins via CO hydrogenation.     

Cu2MoS4/Au Heterostructures with Enhanced Catalase‐Like Activity and Photoconversion Efficiency for Primary/Metastatic Tumors Eradication by Phototherapy‐Induced Immunotherapy

Photoimmunotherapy can not only effectively ablate the primary tumor but also trigger strong antitumor immune responses against metastatic tumors by inducing immunogenic cell death. Herein, Cu₂MoS₄ (CMS)/Au heterostructures are constructed by depositing plasmonic Au nanoparticles onto CMS nanosheets, which exhibit enhanced absorption in near‐infrared (NIR) region due to the newly formed mid‐gap state across the Fermi level based on the hybridization between Au 5d orbitals and S 3p orbitals, thus resulting in more excellent photothermal therapy and photodynamic therapy (PDT) effect than single CMS upon NIR laser irradiation. The CMS and CMS/Au can also serve as catalase to effectively relieve tumor hypoxia, which can enhance the therapeutic effect of O₂‐dependent PDT. Notably, the NIR laser‐irradiated CMS/Au can elicit strong immune responses via promoting dendritic cells maturation, cytokine secretion, and activating antitumor effector T‐cell responses for both primary and metastatic tumors eradication. Moreover, CMS/Au exhibits outstanding photoacoustic and computed tomography imaging performance owing to its excellent photothermal conversion and X‐ray attenuation ability. Overall, the work provides an imaging‐guided and phototherapy‐induced immunotherapy based on constructing CMS/Au heterostructures for effectively tumor ablation and cancer metastasis inhibition.     

A Tumor‐Microenvironment‐Activated Nanozyme‐Mediated Theranostic Nanoreactor for Imaging‐Guided Combined Tumor Therapy

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme‐mediated 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) loaded ABTS@MIL‐100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging‐guided combined tumor therapy. The as‐constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme‐mediated “two‐step rocket‐launching‐like” process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H₂O₂ level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor‐triggered PTT. More importantly, the H₂O₂‐activated and acid‐enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme‐involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.     

Carrier-Free H2O2 Self-Supplier for Amplified Synergistic Tumor Therapy

Chemodynamic therapy (CDT) utilizes Fenton or Fenton-like reactions to convert hydrogen peroxide (H₂O₂) into cytotoxic hydroxyl radicals (•OH) and draws extensive interest in tumor therapy. Nevertheless, high concentrations of glutathione (GSH) and insufficient endogenous H₂O₂ often cause unsatisfactory therapeutic efficacy. Herein, a GSH-depleting and H₂O₂ self-providing carrier-free nanomedicine that can efficiently load indocyanine green (ICG), β-lapachone (LAP), and copper ion (Cu²⁺) (ICG-Cu²⁺-LAP, LICN) to mediate synergetic photothermal and chemotherapy in enhanced chemodynamic therapy is designed. The results show that  LICNs successfully enter tumors owing to the enhanced permeability and retention effect. Through the reductive intracellular environment, Cu²⁺ in LICN can react with intracellular GSH, alleviate the antioxidant capacity of tumor tissues, and trigger the release of drugs. When LICN is subjected to near-infrared (NIR) irradiation, enhanced photothermal effect and upregulated expression of NAD(P)H quinone oxidoreductase-1 (NQO1) are observed. Meanwhile, the released LAP not only supports chemotherapy but also catalyzes NQO1 and produces sufficient endogenous H₂O₂, thereby increasing the efficiency of Cu⁺-based Fenton-like reaction. Notably, GSH depletion and H₂O₂ self-sufficiency generate sufficient •OH and kill tumor cells with high specificity. Overall, the study provides an innovative strategy to self-regulate GSH and H₂O₂ levels for effective anticancer therapy.     

Promoting Oxygen Evolution Reaction of Co‐Based Catalysts (Co3O4, CoS,CoP, and CoN) through Photothermal Effect

The increase of reaction temperature of electrocatalysts is regarded as an efficient method to improve the oxygen evolution reaction (OER) activity. Herein, it is reported that the electrocatalytic performance of dual functional (i.e., electrocatalytic and photothermal functions) Co₃O₄ can be dramatically improved via its photothermal effect. The operating temperature of the Co₃O₄ electrode is elevated in situ under near infrared (NIR) light irradiation, resulting in enhanced oxygen evolution activity due to its accelerated electrical conductivity, reaction kinetics, and desorption rate of O₂ bubbles from the electrode. In addition, photothermal effect can also enhance the electrocatalytic reaction rates of metal‐doped Co₃O₄ electrodes, indicating that it is able to significantly improve the OER activities of electrodes together with other modification strategies. With the assistance of the photothermal effect, the obtained Ni‐doped Co₃O₄ catalyst requires an extremely low overpotential of 208 mV to achieve a benchmark of 10 mA cm^?2 with a small Tafel slope, superior to most reported Co‐based catalysts. Significantly, the electrocatalytic performance of other electrodes with photothermal effect, such as CoN, CoP, and CoS, are also boosted under NIR light irradiation, indicating opportunities for implementing photothermal enhancement in electrocatalytic water splitting.     

FeIII‐Doped Two‐Dimensional C3N4 Nanofusiform: A New O2‐Evolving and Mitochondria‐Targeting Photodynamic Agent for MRI and Enhanced Antitumor Therapy

Local hypoxia in tumors, as well as the short lifetime and limited action region of ¹O₂, are undesirable impediments for photodynamic therapy (PDT), leading to a greatly reduced effectiveness. To overcome these adversities, a mitochondria‐targeting, H₂O₂‐activatable, and O₂‐evolving PDT nanoplatform is developed based on Fe^III‐doped two‐dimensional C₃N₄ nanofusiform for highly selective and efficient cancer treatment. The ultrahigh surface area of 2D nanosheets enhances the photosensitizer (PS) loading capacity and the doping of Fe^III leads to peroxidase mimetics with excellent catalytic performance towards H₂O₂ in cancer cells to generate O₂. As such tumor hypoxia can be overcome and the PDT efficacy is improved, whilst at the same time endowing the PDT theranostic agent with an effective T ₁‐weighted in vivo magnetic resonance imaging (MRI) ability. Conjugation with a mitochondria‐targeting agent could further increase the sensitivity of cancer cells to ¹O₂ by enhanced mitochondria dysfunction. In vitro and in vivo anticancer studies demonstrate an outstanding therapeutic effectiveness of the developed PDT agent, leading to almost complete destruction of mouse cervical tumor. This development offers an attractive theranostic agent for in vivo MRI and synergistic photodynamic therapy toward clinical applications.     

Rhenium‐188 Labeled Tungsten Disulfide Nanoflakes for Self‐Sensitized,Near‐Infrared Enhanced Radioisotope Therapy

Radioisotope therapy (RIT), in which radioactive agents are administered or implanted into the body to irradiate tumors from the inside, is a clinically adopted cancer treatment method but still needs improvement to enhance its performances. Herein, it is found that polyethylene glycol (PEG) modified tungsten disulfide (WS₂) nanoflakes can be easily labeled by ¹⁸⁸Re, a widely used radioisotope for RIT, upon simple mixing. Like other high‐Z elements acting as radiosensitizers, tungsten in the obtained ¹⁸⁸Re‐WS₂‐PEG would be able to absorb ionization radiation generated from ¹⁸⁸Re, enabling ‘‘self‐sensitization’’ to enhance the efficacy of RIT as demonstrated in carefully designed in vitro experiments of this study. In the meanwhile, the strong NIR absorbance of WS₂‐PEG could be utilized for NIR light‐induced photothermal therapy (PTT), which if applied on tumors would be able to greatly relieve their hypoxia state and help to overcome hypoxia‐associated radioresistance of tumors. Therefore, with ¹⁸⁸Re‐WS₂‐PEG as a multifunctional agent, which shows efficient passive tumor homing after intravenous injection, in vivo self‐sensitized, NIR‐enhanced RIT cancer treatment is realized, achieving excellent tumor killing efficacy in a mouse tumor model. This work presents a new concept of applying nanotechnology in RIT, by delivering radioisotopes into tumors, self‐sensitizing the irradiation‐induced cell damage, and modulating the tumor hypoxia state to further enhance the therapeutic outcomes.     

Sub‐10‐nm Pd Nanosheets with Renal Clearance for Efficient Near‐Infrared Photothermal Cancer Therapy

Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra‐small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra‐small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface‐functionalized with reduced glutathione (GSH), the SPNS‐GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra‐small Pd nanosheets promising for practical use in photothermal cancer therapy.