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Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu−O2/Cu−O4) via GSH‐responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase‐like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off‐target effects of SACs‐induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis‐associated therapies. [ABSTRACT FROM AUTHOR]

Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu−O2/Cu−O4) via GSH‐responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase‐like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off‐target effects of SACs‐induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis‐associated therapies. [ABSTRACT FROM AUTHOR]

We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2−⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2), with a half‐maximal inhibitory concentration (IC50) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors. [ABSTRACT FROM AUTHOR]

We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2−⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2), with a half‐maximal inhibitory concentration (IC50) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors. [ABSTRACT FROM AUTHOR]

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound‐based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen‐vacancy‐engineered W18O49−x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18O49−x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1O2), superoxide anions (⋅O2−), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron‐hole recombination are incidentally introduced through one‐step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen‐vacancy‐engineered W18O49−x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT. [ABSTRACT FROM AUTHOR]

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound‐based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen‐vacancy‐engineered W18O49−x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18O49−x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1O2), superoxide anions (⋅O2−), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron‐hole recombination are incidentally introduced through one‐step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen‐vacancy‐engineered W18O49−x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT. [ABSTRACT FROM AUTHOR]

The sonodynamic activities of gold nanoparticles (GNPs) with different morphologies, gold nanospheres (GNSs), gold nanoflowers (GNFs) and gold nanorods (GNRs), were explored by multi‐spectroscopic methods, in which the lesion degree of human serum albumin (HSA) was used as assessment index. The results revealed that three GNPs all had certain sonosensitivity but varying from different morphologies. It was also found that GNPs concentration and ultrasonic parameters were all critical influencing factors of sonodynamic injury HSA. Investigating the physical damage mechanism, the results indicated that the secondary and tertiary structure of HSA were compromised by ultrasound (US) combined with GNPs, so that the conformation of HSA was altered and the function was variously disturbed due to GNPs different morphologies. Studying the chemical damage mechanism, the results discovered that the yield of singlet oxygen (1O2) produced by GNPs with various morphologies combined with US was significant difference. Therefore, comprehensively analyzing the research results under different factors, the order of sonodynamic activities of GNPs was GNSs≈GNFs>GNRs. These findings may provide reference for the application of GNPs as sonosensitizers in sonodynamic therapy. [ABSTRACT FROM AUTHOR]

Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS QTANHOH displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC50) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular‐targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models. [ABSTRACT FROM AUTHOR]