Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis via Nrf2-Dependent Macrophage Reprogramming.

Inflammatory bowel disease (IBD) is one of the main factors leading to colitis-associated colorectal cancer (CAC). Therefore, it is critical to develop an effective treatment for IBD to prevent secondary colorectal carcinogenesis. M2 macrophages play crucial roles in the resolution phase of intestinal inflammation. However, traditional drugs rarely target intestinal M2 macrophages, and they are not easily cleared. Gold nanoclusters are known for their in vivo safety and intrinsic biomedical activities. In this study, a glutathione-protected gold nanocluster is synthesized and evaluated, namely, GA. Interestingly, GA specifically accumulates in the colon during IBD. Furthermore, GA not only promotes M2 differentiation of IL-4-treated peritoneal macrophages but also reprograms macrophage polarization from M1 to M2 in a pro-inflammatory environment. Mechanistically, this regulatory effect is exerted through activating the antioxidant Nrf2 signaling pathway, but not traditional STAT6. When applied in IBD mice, we found that GA elevates M2 macrophages and alleviates IBD in an Nrf2-dependent manner, evidenced by the abolished therapeutic effect upon Nrf2 inhibitor treatment. Most importantly, GA administration significantly suppresses AOM/DSS-induced CAC, without causing obvious tissue damage, providing critical evidence for the potential application of gold nanoclusters as nanomedicine for the treatment of IBD and CAC.

Observation of the protein expression level via naked eye: Pt clusters catalyze non-color molecules into brown-colored molecules in cells.

α v ß 3 is overexpressed in various tumor cells and plays a key role in tumor genesis, invasion, and metastasis. Therefore, it is of great significance to precisely detect the α v ß 3 level in cells via a simple method. For this purpose, we have constructed a peptide-coated platinum (Pt) cluster. Due to its bright fluorescence, well-defined Pt atom numbers, and peroxidase-like catalytic activity, this cluster can be used to evaluate α v ß 3 levels in cells by fluorescence imaging, inductively coupled plasma mass spectrometry (ICP-MS), and catalytic amplification of visual dyes, respectively. In this report, the expression level of α v ß 3 in living cells is well-detected by the naked eye under an ordinary light microscope when the Pt cluster binds to αvß3 in cells and catalyzes non-color 3,3'-diaminobenzidine (DAB) into brown-colored molecules in situ. Moreover, SiHa, HeLa, and 16HBE cell lines with different α v ß 3 expression levels can be visually distinguished by the peroxidase-like Pt clusters. This research will provide a reliable method for the simple detection of α v ß 3 levels in cells.

Hydroquinone colorimetric sensing based on platinum deposited on CdS nanorods as peroxidase mimics.

Pt deposited on CdS nanorods (Pt/CdS) have been prepared via the UV light photoreduction method. The Pt/CdS nanocomposites possess highly significant peroxidase-like activity with the assistance of the colorless substrate 3,3,5,5-tetramethylbenzidine (TMB). In the presence of peroxidase mimic Pt/CdS, TMB is quickly oxidized into a typical blue product (oxTMB, which has an obvious absorption at 652 nm) by H2O2 only in 3 min, which is easily detected visually. The catalytic activity of Pt/CdS originates from the accelerated electron transfer between the reactants. Combining the peroxidase-like activity of Pt/CdS with the blue change of TMB, a fast colorimetric sensing platform for detection of H2O2 has been constructed with a linear range 0.10-1.00 mM and a detection limit of 45.5 µM. The platform developed is further used to detect hydroquinone (HQ) in the range1.0-10 µM with a lower detection limit of 0.165 µM. The colorimetric platform has a potential to detect HQ residue in real water samples with recoveries ranging from 83.56 to 91.76%. Graphical abstract.

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.

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.