Precise design of dual active-site catalysts for synergistic catalytic therapy of tumors.

A proven and promising method to improve the catalytic performance of single-atom catalysts through the interaction between bimetallic atoms to change the active surface sites or adjust the catalytic sites of reactants is reported. In this work, we used an iron-platinum bimetallic reagent as the metal source to precisely synthesise covalent organic framework-derived diatomic catalysts (FePt-DAC/NC). Benefiting from the coordination between the two metal atoms, the presence of Pt single atoms can successfully regulate Fe-N3 activity. FePt-DAC/NC exhibited a stronger ability to catalyze H2O2 to produce toxic hydroxyl radicals than Fe single-atom catalysts (Fe-SA/NC) to achieve chemodynamic therapy of tumors (the catalytic efficiency improved by 186.4%). At the same time, under the irradiation of an 808 nm laser, FePt-DAC/NC exhibited efficient photothermal conversion efficiency to achieve photothermal therapy of tumors. Both in vitro and in vivo results indicate that FePt-DAC/NC can efficiently suppress tumor cell growth by a synergistic therapeutic effect with photothermally augmented nanocatalytic therapy. This novel bimetallic dual active-site monodisperse catalyst provides an important example for the application of single-atom catalysts in the biomedical field, highlighting its promising clinical potential.

Exogenous abscisic acid and sodium nitroprusside regulate flavonoid biosynthesis and photosynthesis of Nitraria tangutorum Bobr in alkali stress.

Abscisic acid (ABA) and nitric oxide (NO) are involved in mediating abiotic stress-induced plant physiological responses. Nitraria tangutorum Bobr is a typical salinized desert plant growing in an arid environment. In this study, we investigated the effects of ABA and NO on N.tangutorum seedlings under alkaline stress. Alkali stress treatment caused cell membrane damage, increased electrolyte leakage, and induced higher production of reactive oxygen species (ROS), which caused growth inhibition and oxidative stress in N.tangutorum seedlings. Exogenous application of ABA (15µm) and Sodium nitroprusside (50µm) significantly increased the plant height, fresh weight, relative water content, and degree of succulency in N.tangutorum seedlings under alkali stress. Meanwhile, the contents of ABA and NO in plant leaves were significantly increased. ABA and SNP can promote stomatal closure, decrease the water loss rate, increase leaf surface temperature and the contents of osmotic regulator proline, soluble protein, and betaine under alkali stress. Meanwhile, SNP more significantly promoted the accumulation of chlorophyll a/b and carotenoids, increased quantum yield of photosystem II (φPSII) and electron transport rate (ETRII) than ABA, and decreased photochemical quenching (qP), which improved photosynthetic efficiency and accelerated the accumulation of soluble sugar, glucose, fructose, sucrose, starch, and total sugar. However, compared with exogenous application of SNP in the alkaline stress, ABA significantly promoted the transcription of NtFLS/NtF3H/NtF3H/NtANR genes and the accumulation of naringin, quercetin, isorhamnetin, kaempferol, and catechin in the synthesis pathway of flavonoid metabolites, and isorhamnetin content was the highest. These results indicate that both ABA and SNP can reduce the growth inhibition and physiological damage caused by alkali stress. Among them, SNP has a better effect on the improvement of photosynthetic efficiency and the regulation of carbohydrate accumulation than ABA, while ABA has a more significant effect on the regulation of flavonoid and anthocyanin secondary metabolite accumulation. Exogenous application of ABA and SNP also improved the antioxidant capacity and the ability to maintain Na+/K+ balance of N. tangutorum seedlings under alkali stress. These results demonstrate the beneficial effects of ABA and NO as stress hormones and signaling molecules that positively regulate the defensive response of N. tangutorum to alkaline stress.

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy.

Recently, disulfiram (DSF), approved by the FDA as an anti-alcoholic drug, has been proved as an effective antitumor drug after chelating with Cu2+. To overcome the shortage of intracellular Cu2+, we have constructed a dual gate-controlled intelligent nanoreactor (HA-DSF@HCuS@FePtMn, HDHF) via the ingenious combination of hollow copper sulfide (HCuS) nanoparticles, DSF and FePtMn nanocrystals. HDHF has a NIR-actuated gate and enzyme-actuated gate that could be opened in the hyaluronidase-abundant tumor microenvironment with NIR laser irradiation to trigger drug (DSF/FePtMn) release and synergistic therapy. Moreover, the FePtMn nanocrystals could continuously release Fe2+, which could catalyze H2O2 into highly cytotoxic hydroxyl radicals (˙OH), triggering chemodynamic therapy (CDT). When exposed to NIR laser, HCuS could collapse and release Cu2+, which could immediately chelate with DSF, forming the effective anticancer drug (Cu(DTC)2) and enabling DSF-based chemotherapy. More importantly, the efficient photothermal therapy (PTT) effect of HCuS could accelerate the FePtMn-based CDT and the release of Cu2+/DSF, improving tumor treatment efficiency. Thus, this study represents a distinctive paradigm of a dual gate-controlled intelligent nanoreactor enabled PTT-augmented DSF-based chemotherapy and FePtMn-based CDT for cancer nanotherapy.

Oncocyte Membrane-Camouflaged Multi-Stimuli-Responsive Nanohybrids for Synergistic Amplification of Tumor Oxidative Stresses and Photothermal Enhanced Cancer Therapy.

The combination of various therapeutic modalities has received considerable attention for improving antitumor performance. Herein, an innovative nanohybrid, namely CaO2@FePt-DOX@PDA@CM (CFDPM), was developed for synergistic chemotherapy/chemodynamic therapy/Ca2+ overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy. Camouflage of the 4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue. Ca2+, released from CaO2, could lead to mitochondrial dysfunction and facilitate the production of reactive oxygen species to amplify intracellular oxidative stress. Meanwhile, the increase of H2O2 concentration could enhance the efficiency of the chemodynamic therapy (CDT). Moreover, the hypoxic condition could be alleviated remarkably, which is attributed to the sufficient O2 supply by CaO2, resulting in the suppression of drug resistance and promotion of the chemotherapeutic effect. The nanohybrids involving Ca2+ overloading/CDT/chemotherapy could synergistically amplify the tumor oxidative stresses and remarkably aggravate the death of cancer cells. Significantly, the excellent photothermal conversion performance of CFDPM could further promote the tumoricidal effect. The in vitro and in vivo studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue, which would open a valuable avenue for effective cancer treatment.

Precise Design of Atomically Dispersed Fe, Pt Dinuclear Catalysts and Their Synergistic Application for Tumor Catalytic Therapy.

Recently, extending single-atom catalysts from mono- to binary sites has been proved to be a promising way to realize more efficient chemical catalytic processes. In this work, atomically dispersed Fe, Pt dinuclear catalysts ((Fe, Pt)SA-N-C) with an ca. 2.38 Šdistance for Fe1 (Fe-N3) and Pt1 (Pt-N4) could be precisely controlled via a novel secondary-doping strategy. In response to tumor microenvironments, the Fe-N3/Pt-N4 moieties exhibited synergistic catalytic performance for tumor catalytic therapy. Due to its beneficial microstructure and abundant active sites, the Fe-N3 moiety effectively initiated the intratumoral Fenton-like reaction to release a large amount of toxic hydroxyl radicals (•OH), which further induced tumor cell apoptosis. Meanwhile, the bonded Pt-N4 moiety could also enhance the Fenton-like activity of the Fe-N3 moiety up to 128.8% by modulating the 3d electronic orbitals of isolated Fe-N3 sites. In addition, the existence of amorphous carbon revealed high photothermal conversion efficiency when exposed to an 808 nm laser, which synergistically achieved an effective oncotherapy outcome. Therefore, the as-obtained (Fe, Pt)SA-N-C-FA-PEG has promising potential in the bio-nanomedicine field for inhibiting tumor cell growth in vitro and in vivo.

Advances in FePt-involved nano-system design and application for bioeffect and biosafety.

The rapid development and wide application of nanomaterial-involved theranostic agents have drawn surging attention for improving the living standard of humankind and healthcare conditions. In this review, recent developments in the design, synthesis, biocompatibility evaluation and potential nanomedicine applications of FePt-involved nano-systems are summarized, especially for cancer theranostic and biological molecule detection. The in vivo multi-model imaging capability is discussed in detail, including magnetic resonance imaging and computed tomography. Furthermore, we highlight the significant achievements of various FePt-involved nanotherapeutics for cancer treatment, such as drug delivery, chemodynamic therapy, photodynamic therapy, radiotherapy and immunotherapy. In addition, a series of FePt-involved nanocomposites are also applied for biological molecule detection, such as H2O2, glucose and naked-eye detection of cancer cells. Ultimately, we also summarize the challenges and prospects of FePt-involved nano-systems in nanocatalytic medicine. This review is expected to give a general pattern for the development of FePt-involved nano-systems in the field of nanocatalytic medicine and analytical determination.

A flowerlike FePt/MnO2/GOx-based cascade nanoreactor with sustainable O2 supply for synergistic starvation-chemodynamic anticancer therapy.

The development of versatile nanotheranostic agents has received increasing interest in cancer treatment. Herein, in this study, we rationally designed and prepared a novel flowerlike multifunctional cascade nanoreactor, BSA-GOx@MnO2@FePt (BGMFP), by integrating glucose oxidase (GOx), manganese dioxide (MnO2) and FePt for synergetic cancer treatment with satisfying therapeutic efficiency. In an acidic environment, intratumoral H2O2 could be decomposed to O2 to accelerate the consumption of glucose catalyzed by GOx to induce cancer starvation. Moreover, the accumulation of gluconic acid and H2O2 generated along with the consumption of glucose would in turn promote the catalytic efficiency of MnO2 and boost O2 evolution, which could enhance the efficiency of starvation therapy. Moreover, FePt as an excellent Fenton agent could simultaneously convert H2O2 to the toxic hydroxyl radical (˙OH), subsequently resulting in amplified intracellular oxidative stress and cell apoptosis. Therefore, BGMFP could catalyze a cascade of intracellular biochemical reactions and optimize the unique properties of MnO2, GOx and FePt via mutual promotion of each other to realize O2 supply, chemodynamic therapy (CDT) and starvation therapy. The anticancer results in vitro and in vivo demonstrated that BGMFP possessed remarkable tumor inhibition capacity through enhancing the starvation therapy and CDT. It is appreciated that BGMFP could be a promising platform for synergetic cancer treatment.

Resorufin-based responsive probes for fluorescence and colorimetric analysis.

The fluorescence imaging technique has attracted increasing attention in the detection of various biological molecules in situ and in real-time owing to its inherent advantages including high selectivity and sensitivity, outstanding spatiotemporal resolution and fast feedback. In the past few decades, a number of fluorescent probes have been developed for bioassays and imaging by exploiting different fluorophores. Among various fluorophores, resorufin exhibits a high fluorescence quantum yield, long excitation/emission wavelength and pronounced ability in both fluorescence and colorimetric analysis. This fluorophore has been widely utilized in the design of responsive probes specific for various bioactive species. In this review, we summarize the advances in the development of resorufin-based fluorescent probes for detecting various analytes, such as cations, anions, reactive (redox-active) sulfur species, small molecules and biological macromolecules. The chemical structures of probes, response mechanisms, detection limits and practical applications are investigated, which is followed by the discussion of recent challenges and future research perspectives. This review article is expected to promote the further development of resorufin-based responsive fluorescent probes and their biological applications.

Core-shell FePt-cube@covalent organic polymer nanocomposites: a multifunctional nanocatalytic agent for primary and metastatic tumor treatment.

Metastasis and spread are currently the main factors leading to high mortality of cancer, so developing a synergetic antitumor strategy with high specificity and hypotoxicity is in urgent demand. Based on the design concept of "nanocatalytic medicine", multifunctional nanotherapeutic agent FePt@COP-FA nanocomposites (FPCF NCs) are developed for cancer treatment. Specifically, in the tumor microenvironment (TME), FePt could catalyze intracellular over-expressed H2O2 to generate highly active hydroxyl radicals (˙OH), which could not only induce the apoptosis of tumor cells, but also activate the "ferroptosis" pathway resulting in the lipid peroxide accumulation and ferroptotic cell death. Moreover, owing to the excellent photothermal effect, the FPCF NCs could effectively ablate primary tumors under near-infrared (NIR) laser irradiation and produce numerous tumor-associated antigens in situ. With the assistance of a checkpoint blockade inhibitor, anti-CTLA4 antibody, the body's specific immune response would be initiated to inhibit the growth of metastatic tumors. In particular, such synergistic therapeutics could produce an effective immunological memory effect, which could prevent tumor metastasis and recurrence again. In summary, the FPCF NC is an effective multifunctional antitumor therapeutic agent for nanocatalytic/photothermal/checkpoint blockade combination therapy, which exhibits great potential in nanocatalytic anticancer therapeutic 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.

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.

A novel theranostic nano-platform (PB@FePt-HA-g-PEG) for tumor chemodynamic-photothermal co-therapy and triple-modal imaging (MR/CT/PI) diagnosis.

The construction of multi-functional oncotherapy nano-platforms combining diagnosis and therapy remains a tough challenge. Prussian blue nano-cubes with optimized particle size were applied as photothermal agents and loaded with FePt NPs, effective ferroptosis agents, on the surface via an in situ reduction strategy. To attain the goal of precise medicine, hyaluronic acid was wrapped around the surface of the nanocomposites (PB@FePt NCs) for highly specific recognition of tumor cells. Finally, we successfully designed and fabricated a nano-agent (PB@FePt-HA-g-PEG NCs) to serve as a versatile nano-platform with both highly specific targeting ability for chemodynamic-photothermal co-therapy and triple-modal imaging (magnetic resonance/computed tomography/photothermal imaging) capability. Via intravenous injection, the as-constructed oncotherapy nano-platform could effectively ablate 4T1 tumor xenografts with excellent biocompatibility for chemodynamic-photothermal co-therapy. In this study we conducted a reasonable exploration to design multi-functional oncotherapy nano-platforms combining multiplexed imaging diagnosis and high therapeutic performance, which provides an innovative paradigm for precision cancer treatment.

Time-gated luminescence probe for ratiometric and luminescence lifetime detection of Hypochorous acid in lysosomes of live cells.

Time-gated luminescence (TGL) probes based on lanthanide complexes have appealed wide attention in the detection of biologically relevant analytes because of their inimitable photophysical properties. In this work, a TGL probe (TR-HOCl) based on intramolecular Förster resonance energy transfer (FRET) system for specific determination of hypochlorous acid (HOCl) was designed and synthesized, in which a rhodamine derivative (energy acceptor) was conjugated to a luminescent Tb3+ complex (energy donor). After reacting with HOCl, the Tb3+ emission of TR-HOCl at 540 nm declined while the rhodamine emission at 580 nm increased, which leaded to an increase of the TGL intensity ratio of rhodamine to Tb3+ complex (I560/I540) up to ~9-fold. The dose-dependent increase of I560/I540 gives a nice linearity in HOCl concentration range of 0.5-45 µM. The detection limit of for HOCl was determined to be 0.34 µM. Interestingly, the average luminescence lifetime of the Tb3+ emission decreased (from 588 µs to 254 µs) accompanied with the FRET process and the value gave a fine linearity to the variation of HOCl concentration. Additionally, TR-HOCl showed great selectivity for recognition of HOCl over other ROS, RNS, biothiols and other interference. These properties endow TR-HOCl to be conveniently applied for high accurate recognition of HOCl with ratiometric TGL and luminescence lifetime dual-signal output. Finally, TR-HOCl was successfully applied for the TGL determination of HOCl in HepG2 cells. The co-localization experiments of TR-HOCl with LysoSensor Green revealed the lysosome-localizing property of the probe in live cells. The study demonstrated that TR-HOCl could be a competent tool for investigating roles of HOCl in various physiological processes.

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@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.

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.

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.

Development of a novel FePt-based multifunctional ferroptosis agent for high-efficiency anticancer therapy.

Ferroptosis as an emerging mechanism has become a research hotspot for killing cancer cells. In this work, a novel ferroptosis agent, FePt-PTTA-Eu3+-FA (FPEF), was rationally designed by harnessing the luminescent lanthanide complexes PTTA-Eu3+ and folic acid (FA) in FePt nanoparticles. FePt-Based nanomaterials have potential applications in magnetic resonance imaging/computed tomography (MRI/CT) in clinical diagnosis and have excellent capacity to induce cancer cell death. Mechanistic studies of FPEP showed that the FePt induced cancer cell death was affirmed as the ferroptosis mechanism. To the best of our knowledge, it will be the first report that proves the existence of the ferroptosis process in FePt NPs. The in vitro tests of FPEF demonstrated that the as-prepared NPs exhibit a satisfactory anticancer effect towards FA-positive tumor cells including 4T1, MCF-7 and HeLa cells. The in vivo studies using tumor-bearing balb/c mice revealed that the FPEF NPs could significantly inhibit tumor progression. Such all-in-one therapeutic strategies have great potential in early diagnosis, prognosis and treatment of cancer.

Construction of a multifunctional nanoprobe for tumor-targeted time-gated luminescence and magnetic resonance imaging in vitro and in vivo.

A dual-modal fluorescence-magnetic resonance imaging technique has gained tremendous attention for its potential in the dawning era of early diagnosis of tumors with high accuracy. In this study, a facile approach has been developed to prepare a tumor-targetable nanoprobe, PTTA-Eu3+-CoFeO-FA nanoparticles, for dual-modal time-gated luminescence (TGL)-magnetic resonance (MR) imaging of tumor cells in vitro and in vivo. The multifunctional nanoprobe was constructed by coating a tumor-targeting molecule, folic acid (FA), and a luminescent Eu3+ complex, PTTA-Eu3+, onto the surface of cobalt/iron oxide (CoFeO) nanoparticles. The as-prepared PTTA-Eu3+-CoFeO-FA nanoparticles are well dispersed in water with good biocompatibility, strong long-lived luminescence as well as pronounced transverse relaxivity. The in vitro study reveals that the nanoprobe works well as an effective luminescent probe to achieve the targeted TGL imaging of RAW 264.7 cells without the interference of background fluorescence, and the results of in vivo dual-modal TGL-MR imaging indicate that the fabricated nanoprobe can be preferentially accumulated in the tumor to effectively enhance the signals of T2-weighted MR imaging and TGL imaging. The research achievements will contribute to the development of new dual-modal fluorescence-MR nanoprobes for application in clinical diagnosis and therapy of tumors.

High-performance electrochemical sensing of circulating tumor DNA in peripheral blood based on poly-xanthurenic acid functionalized MoS2 nanosheets.

A high-performance sensing platform based on poly-xanthurenic acid (PXA) film functionalized MoS2 nanosheets was developed for electrochemical detection of circulating tumor DNA in peripheral blood. The MoS2 nanosheets were obtained using a simple ultrasonic method from bulk MoS2. The physical adsorption between MoS2 and aromatic XA monomers effectively improved the electropolymerization efficiency, accompanied with an increased electrochemical response of PXA. The obtained PXA/MoS2 nanocomposite not only served as a substrate for DNA immobilization but also reflected the electrochemical transduction originating from DNA immobilization and hybridization without any complex labelling processes or outer indicators. The immobilization of the probe ssDNA was achieved via noncovalent assembly due to the π-π interaction between PXA and DNA bases. After the hybridization of the probe ssDNA with the target DNA, the formation of helix structure induced the resulted dsDNA to be released from the surface of the PXA/MoS2 nanocomposite. The detection limit of this constructed DNA biosensor was calculated in the linear target DNA concentrations range from 1.0 × 10-16 mol/L to 1.0 × 10-10 mol/L and it was found to be 1.8 × 10-17 mol/L.