FeSA­Ir/Metallene Nanozymes Induce Sequential Ferroptosis­Pyroptosis for Multi­Immunogenic Responses Against Lung Metastasis.

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O2 and 1O2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition.

Capture and separation of circulating tumor cells using functionalized magnetic nanocomposites with simultaneous in situ chemotherapy.

Circulating tumor cells (CTCs) are a type of rare cell that are firstly shed from solid tumors and then exist in the bloodstream. The effective capture and separation of CTCs has significant meaning in cancer diagnosis and prognosis. In this study, novel Fe3O4-FePt magnetic nanocomposites (Fe3O4-FePt MNCs) were constructed by integrating face centered cubic (fcc) FePt nanoparticles (NPs) onto the surface of the Fe3O4@SiO2 core. After further modification with NH2-PEG-COOH and the tumor-targeting molecule tLyP-1, the acquired Fe3O4-FePt MNCs possesses excellent biocompatibility and stability and could efficiently target and capture tLyP-1 receptor-positive CTCs. Based on the acidic microenvironment within cancer cells, the FePt layer could rapidly release active Fe2+ ions, which could catalyze H2O2 into reactive oxygen species (ROS) and further induce in situ apoptosis in cancer cells while having no distinct cytotoxicity to normal cells. Moreover, the Fe3O4@SiO2 core with its intrinsic magnetism has huge potential for the bioseparation of CTCs. The in vitro ROS fluorescence imaging experiments and cell capture and separation experiments indicated that the Fe3O4-FePt MNCs could specifically capture and separate cancer cells in the CTCs model and further induce in situ apoptosis. Therefore, the Fe3O4-FePt MNCs could serve as a promising multifunctional nanoseparator for efficiently capturing CTCs and simultaneously inducing in situ chemotherapy.

Characterizing the noncovalent binding behavior of tartrazine to lysozyme: A combined spectroscopic and computational analysis.

Tartrazine is a stable water-soluble azo dye widely used as a food additive, which could pose potential threats to humans and the environment. In this paper, we evaluated the response mechanism between tartrazine and lysozyme under simulated conditions by means of biophysical methods, including multiple spectroscopic techniques, isothermal titration calorimetry (ITC), and molecular docking studies. From the multispectroscopic analysis, we found that tartrazine could effectively quench the intrinsic fluorescence of lysozyme to form a complex and lead to the conformational and microenvironmental changes of the enzyme. The ITC measurements suggested that the electrostatic forces played a major role in the binding of tartrazine to lysozyme with two binding sites. Finally, the molecular docking indicated that tartrazine had specific interactions with the residues of Trp108. The study provides an important insight within the binding mechanism of tartrazine to lysozyme in vitro.

A facile preparation of FePt-loaded few-layer MoS2 nanosheets nanocomposites (F-MoS2-FePt NCs) and their application for colorimetric detection of H2O2 in living cells.

BACKGROUND: Rapid and sensitive detection of H2O2 especially endogenous H2O2 is of great importance for series of industries including disease diagnosis and therapy. In this work, uniform FePt nanoparticles are successfully anchored onto Few-layer molybdenum disulfide nanosheets (F-MoS2 NSs). The powder X-ray diffraction, transmission electron microscopy, UV-Vis spectra and atomic force microscopy were employed to confirm the structure of the obtained nanocomposites (F-MoS2-FePt NCs). The prepared nanocomposites show efficient peroxidase-like catalytic activities verified by catalyzing the peroxidation substrate 4,4'-diamino-3,3',5,5'-tetramethylbiphenyl (TMB) with the existence of H2O2. RESULTS: The optimal conditions of the constructed colorimetric sensing platform is proved as 35 °C and pH 4.2. Under optimal catalytic conditions, the detection limit for H2O2 detection reaches 2.24 µM and the linear ranger is 8 µM to 300 µM. Furthermore, the proposed colorimetric sensing platform was successfully utilized to detect the intracellular H2O2 of cancer cells (MCF-7). CONCLUSIONS: These findings indicated that the F-MoS2-FePt-TMB-H2O2 system provides a potential sensing platform for hydrogen peroxide monitoring in living cells.

Amino porphyrin-peptide assemblies induce ribosome damage and cancer stem cell inhibition for an enhanced photodynamic therapy.

Cancer stem cells (CSCs) are the subpopulation of tumor cells with the properties of tumorigenesis, multilineage differentiation potential and self-renewal, which is the driving force of tumor recurrence and metastasis. However, targeting CSCs is still the main challenge in cancer therapy due to their rapid growth and fast mutation rate. Herein, we developed a simple strategy of photodynamic therapy (PDT) targeting CSCs, dependent on much more abundant ribosomes in CSCs. The interactions between positively charged nanoparticles with negatively charged nucleic acids architectures in cancer cells could lead ribosomes targeting as well as CSCs targeting. The co-assembly of simple amino porphyrin (m-TAPP) with short peptide (Fmoc-L3-OMe) formed nanoparticles (NPs) with good biocompatibility and photoactivity, became positively charged due to low pH value of tumour microenvironment, and efficiently accessed cancer cell ribosome, approached cancer cell nuclei, therefore enriched in the fast-amplifying CSCs. The inhibitive effect on CSCs by m-TAPP assemblies was verified by the significant reduction of CSCs markers CD44, CD133 and ribosome amount in cancer cells and tissues. Upon light irradiation, the NPs induced ROS generation to provoke destructive cancer cell ribosome damage and subsequent apoptosis to prevent tumor growth markedly. Based on the assemblies of small organic molecules, our study not only achieves ribosome degradation induced cancer cells apoptosis, but also indicates new possibility of performing CSCs targeting PDT.

Assembled small organic molecules for photodynamic therapy and photothermal therapy.

As a worldwide major public health problem, cancer is one of the leading causes of death. Effective treatment of cancer is an important challenge. Therefore, photodynamic therapy (PDT) and photothermal therapy (PTT) have been widely applied as anti-tumour strategies due to their high-performance and limited side effects. Inspired by natural supramolecular architectures, such as cytochromes and photosystems, the hierarchical supramolecular assembly of small organic molecules has been developed for their use as photosensitizers or photothermal agents for PDT and PTT, respectively. In this manuscript, we will summarize the recent progress of PDT and PTT based on the assembly of small organic molecules.

A novel multifunctional FePt/BP nanoplatform for synergistic photothermal/photodynamic/chemodynamic cancer therapies and photothermally-enhanced immunotherapy.

A new multi-modal therapy agent, FePt/BP-PEI-FA nanoplatform, with FePt nanoparticles (FePt NPs) loaded onto ultrathin black phosphorus nanosheets (BPNs), has been constructed to enhance synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) that target primary tumors. In this work, BPNs exhibit excellent photothermal and photodynamic behaviors under different wavelength laser irradiation. After polyethylenimine (PEI) modification, FePt NPs with sizes of 3-4 nm are uniformly attached onto the surface of modified BPNs via electrostatic adsorption. FePt NPs, as a ferroptosis agent, can transform endogenous H2O2 into reactive oxygen species (ROS) through the Fenton reaction, ultimately inducing cell death. Based on magnetic resonance imaging (MR) and thermal imaging, the as-prepared FePt/BP-PEI-FA NCs can inhibit tumor growth by achieving synergistic therapies. More significantly, combined with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade, FePt/BP-PEI-FA NC-induced PTT can control both primary and untreated distant tumors' growth. Therefore, FePt/BP-PEI-FA NCs is a potential multifunctional nanoagent for effective anti-tumor applications.

Ultrasmall Ternary FePtMn Nanocrystals with Acidity-Triggered Dual-Ions Release and Hypoxia Relief for Multimodal Synergistic Chemodynamic/Photodynamic/Photothermal Cancer Therapy.

Multimodal imaging-guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn-Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe2+ to catalyze H2 O2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H2 O2 ) into O2 to overcome the tumor hypoxia barrier. Released O2 is further catalyzed into 1 O2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual-ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O2 -based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual-ROS oxidization to suppress solid tumor remarkably. Additionally, Mn2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T1 -weighted magnetic resonance (MR) imaging) and Fe-synergistic transverse relaxivity (T2 -weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging-guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.

FePt@MnO-Based Nanotheranostic Platform with Acidity-Triggered Dual-Ions Release for Enhanced MR Imaging-Guided Ferroptosis Chemodynamic Therapy.

Reactive oxygen species (ROS)-based anticancer therapy methods were heavily dependent on specific tumor microenvironments such as acidity and excess hydrogen peroxide (H2O2). In this work, an acidity-sensitive nanotheranostic agent (FePt@MnO)@DSPE-PEG5000-FA (FMDF NPs)  was successfully constructed for MR imaging guided ferroptosis chemodynamic therapy (FCDT) of cancer. The FMDF NPs could specifically target folic acid (FA) receptor-positive tumor cells (HeLa etc.) and induce ferroptosis efficiently by rapidly releasing active Fe2+ to catalyze intracellular H2O2 into ROS based on Fenton reaction. On the other hand, the Mn2+ could also be released due to acidity  and further coordinate with GSH to enhance the longitudinal-transverse relaxivity (T1/T2-weighted MR imaging), which could obviously strengthen the contrast distinction between solid tumors and the surrounding tissue to accurately real-time monitor the tumor location. Furthermore, the in vivo anticancer study revealed that the growth of solid tumor models could be suppressed remarkably after treating with FMDF NPs and no obvious damage to other major organs. Therefore, the FMDF NPs were competent simultaneously as an enhanced imaging diagnosis contrast agent and efficient therapy agent for promoting more precise and effective treatment in the bionanomedicine field.

Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy.

The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine-guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.

FePt nanoparticles-decorated graphene oxide nanosheets as enhanced peroxidase mimics for sensitive response to H2O2.

Bimetallic-based nanoparticles usually display improved catalytic performance compared to monometallic counterparts. Herein, the well-dispersed FePt nanoparticles decorated on the surface of graphene oxide (GO) nanosheets have been successfully synthesized by a simple polyol protocol method. The FePt/GO nanocomposites were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive spectrometer (EDS), magnetic property measurement system (MPMS), and Fourier transform infrared spectra (FT-IR), respectively. Interestingly, FePt/GO nanocomposites demonstrated the highly intrinsic peroxidase-like activity and can rapidly catalyze to oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) into a blue product oxidized TMB (oxTMB), in the presence of H2O2 only in 30 s observed by the naked eye. Electron spin resonance (ESR) revealed that the underlying catalytic mechanism of FePt/GO nanocomposites was attributed to the generation of hydroxyl radicals (OH) from decomposing of H2O2, due to the synergistic effect between FePt nanoparticles and GO nanosheets. Moreover, H2O2 can be detected over a wide linear detection range of 0.03-0.5 mM with a detection limit of 2.2 × 10-5 M. Based on the mimic enzyme FePt/GO, a colorimetric ultrasensitive H2O2 sensor was constructed with the help of TMB in buffer solution.