A novel carbazole-pyrimidine-based dual mode fluorescent probe for detection of acidic and basic pH in biological systems.

pH balance is an important factor in regulating the internal environment of body and maintaining the normal physiological activities, but pH cannot be detected in vivo without damaging the tissue. It is important to develop a pH probe with low toxicity, high sensitivity and targeting of organelles. In this research, a novel carbazole-pyrimidine-based probe PKZP was designed from 2-hydroxyl-3-pinanone which was derived from natural monoterpene α-pinene for detecting both acidic and basic pH in vivo.

A CIA strategy with eminent drug-loading capacities for tumor ferroptosis-gas synergistic therapy.

: A common challenge of drug loading and delivery using magnetic resonance imaging (MRI) contrast agents (CAs) is the tendency of aggregation and precipitation at high drug loading conditions. Herein, we propose a generic strategy of controlled ideal aggregation (CIA) to restrict the tendency. : Fe, β-Lapachone (LAP), brequinar (BQR), or Sorafenib (SOR) was respectively loaded onto Gd poly (acrylic acid) macrochelate (GP), an MRI CA, in the hollow core of nitrite-modified hollow mesoporous organosilica nanoparticles (HMON-SNO).

Comparison of the effects of pectin with different esterification degrees on the thermal aggregation of wheat glutenin and gliadin.

Our previous study found that pectin with different degrees of esterification (DE) could affect the thermal aggregation of gluten, but the mechanism was not clear. Analyzing the thermal aggregation of glutenin and gliadin supplemented with pectin can clarify this mechanism. With the increase of temperature, the particle size, disulfide bonds and β-sheet of glutenins increased, the surface hydrophobicity (H) and fluorescence intensity decreased, and the network gradually aggregated, but the change trend of gliadins was opposite.

Carbazole-pyrimidine-based novel ratiometric fluorescent probe with large Stokes shift for detection of hydrazine in real environments and organisms.

Widespread application of hydrazine results in serious harm on the natural environments and human health because of its highly toxic, mutagenic, carcinogenic and teratogenic properties. Hence, it is very emergent to develop a convenient and efficient method for detection of hydrazine existed in real environments and living organisms. In this work, a novel ratiometric fluorescent probe PKZ-IN from the natural monoterpenoid 2-hydroxy-3-pinanone was designed and synthesized to detect trace hydrazine.

A Turbo-Charging System-Like Contrast Agent for MRI-Guided STING Pathway-Activated Cancer Immunotherapy.

To overcome the problems of Gd-based contrast agents (GBCAs) (nephrotoxicity and brain deposition) and stimulator of interferon genes (STING) agonists (poor stability, low delivery efficiency, and potential toxicity), in this study, a Turbo-charging system-like GBCA is designed and constructed for magnetic resonance imaging (MRI) guided STING pathway-activated cancer immunotherapy. Poly(acrylic acid) (PAA) is used to coordinate with Gd, forming a Gd/PAA macrochelate. Both Gd/PAA macrochelate and SR717 are conjugated to cystamine (CA) to obtain SR717-CA@Gd/PAA self-assembled nanoparticles (SAN), which are termed as Turbo S because of its similarity with the Turbo-charging system of cars.

Cyclic catalysis of intratumor Fe initiated by a hollow mesoporous iron sesquioxide nanoparticle for ferroptosis therapy of large tumors.

Numerous nanoparticles have been utilized to deliver Fe for tumor ferroptosis therapy, which can be readily converted to Fevia Fenton reactions to generate hydroxyl radical (•OH). However, the ferroptosis therapeutic efficacy of large tumors is limited due to the slow conversion of Fe to Fevia Fenton reactions. Herein, a strategy of intratumor Fe cyclic catalysis is proposed for ferroptosis therapy of large tumors, which was realized based on our newly developed hollow mesoporous iron sesquioxide nanoparticle (HMISN).

Hollow mesoporous calcium peroxide nanoparticles for drug-free tumor calcicoptosis therapy.

Calcium ions (Ca) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy.

A strategy of "adding fuel to the flames" enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy.

Cuproptosis in antitumor therapy faces challenges from copper homeostasis efflux mechanisms and high glutathione (GSH) levels in tumor cells, hindering copper accumulation and treatment efficacy. Herein, we propose a strategy of "adding fuel to the flames" for potent antitumor therapy through a self-accelerating cycle of ferroptosis-cuproptosis. Disulfiram (DSF) loaded hollow mesoporous copper-iron sulfide (HMCIS) nanoparticle with conjugation of polyethylene glycol (PEG) and folic acid (FA) (i.

Double-Layered Hollow Mesoporous Cuprous Oxide Nanoparticles for Double Drug Sequential Therapy of Tumors.

Cancer stem cells (CSCs) are one of the determinants of tumor heterogeneity and are characterized by self-renewal, high tumorigenicity, invasiveness, and resistance to various therapies. To overcome the resistance of traditional tumor therapies resulting from CSCs, a strategy of double drug sequential therapy (DDST) for CSC-enriched tumors is proposed in this study and is realized utilizing the developed double-layered hollow mesoporous cuprous oxide nanoparticles (DL-HMCONs). The high drug-loading contents of camptothecin (CPT) and all-trans retinoic acid (ATRA) demonstrate that the DL-HMCON can be used as a generic drug delivery system.

A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy.

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm.

Kilogram scale facile synthesis and systematic characterization of a Gd-macrochelate as T-weighted magnetic resonance imaging contrast agent.

To overcome the problems of commercial magnetic resonance imaging (MRI) contrast agents (CAs) (i.e., small molecule Gd chelates), we have proposed a new concept of Gd macrochelates based on the coordination of Gd and macromolecules, e.

MRI-Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis.

Triple negative breast cancer (TNBC) cells have a high demand for oxygen and glucose to fuel their growth and spread, shaping the tumor microenvironment (TME) that can lead to a weakened immune system by hypoxia and increased risk of metastasis. To disrupt this vicious circle and improve cancer therapeutic efficacy, a strategy is proposed with the synergy of ferroptosis, immunosuppression reversal and disulfidptosis. An intelligent nanomedicine GOx-IA@HMON@IO is successfully developed to realize this strategy.

Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy.

Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor.

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway.

Introduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.

Kilogram-Scale Synthesis of Extremely Small Gadolinium Oxide Nanoparticles as a T-Weighted Contrast Agent for Magnetic Resonance Imaging.

Magnetic resonance imaging contrast agents are frequently used in clinics to enhance the contrast between diseased and normal tissues. The previously reported poly(acrylic acid) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GdON-PAA) overcame the problems of commercial Gd chelates, but limitations still exist, i.e.

Ultrathin Clay Nanoparticles-Mediated Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy.

Ferroptosis-triggered immunogenic cell death (ICD) is widely adopted to potentiate the body's antitumor immunity by catalyzing the production of toxic reactive oxygen species (ROS). However, the efficacy of ferroptosis and immunotherapy is greatly restricted by intracellular abundant glutathione (GSH) and immunosuppressive tumor microenvironment (TME). Herein, a facile bottom-up method for solvent-free synthesis of ultrathin manganese (Mn)-based layered double hydroxide nanosheets with high loading efficiency for pro-inflammatory cytokine interferon (IFNγ) (IFNγ/uMn-LDHs) is proposed to mutually reinforce the ferroptosis and systemic immunity.

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for HS-Amplified Ferroptosis Therapy.

Recently, nanozymes with peroxidase (POD)-like activity have shown great promise for ferroptosis-based tumor therapy, which are capable of transforming hydrogen peroxide (HO) to highly toxic hydroxyl radicals (OH). However, the unsatisfactory therapeutic performance of nanozymes due to insufficient endogenous HO and acidity at tumor sites has always been a conundrum. Herein, an ultrasmall gold (Au) @ ferrous sulfide (FeS) cascade nanozyme (AuNP@FeS) with HS-releasing ability constructed with an Au nanoparticle (AuNP) and an FeS nanoparticle (FeSNP) is designed to increase the HO level and acidity in tumor cells the collaboration between cascade reactions of AuNP@FeS and the biological effects of released HS, achieving enhanced OH generation as well as effective ferroptosis for tumor therapy.

An AND Logic Gate for Magnetic-Resonance-Imaging-Guided Ferroptosis Therapy of Tumors.

To improve the magnetic resonance imaging (MRI) efficiency and ferroptosis therapy efficacy of exceedingly small magnetic iron oxide nanoparticles (IO, <5 nm) for tumors via enhancing the sensitivity of tumor microenvironment (TME) responsiveness, inspired by molecular logic gates, a self-assembled IO with an AND logic gate function is designed and constructed. Typically, cystamine (CA) is conjugated onto the end of poly(2-methylthio-ethanol methacrylate) (PMEMA) to generate PMEMA-CA. The PMEMA-CA is grafted onto the surface of brequinar (BQR)-loaded IO to form IO-BQR@PMEMA.

A STING pathway-activatable contrast agent for MRI-guided tumor immunoferroptosis synergistic therapy.

The immunotherapy efficiency of stimulator of interferon genes (STING)-activatable drugs (e.g., 7-ethyl-10-hydroxycamptothecin, SN38) is limited by their non-specificity to tumor cells and the slow excretion of the DNA-containing exosomes from the treated cancer cells.

Exceedingly Small Magnetic Iron Oxide Nanoparticles for T -Weighted Magnetic Resonance Imaging and Imaging-Guided Therapy of Tumors.

Magnetic iron oxide nanoparticles (MIONs) based T -weighted magnetic resonance imaging (MRI) contrast agents (CAs) are liver-specific with good biocompatibility, but have been withdrawn from the market and replaced with Eovist (Gd-EOB-DTPA) due to their inherent limitations (e.g., susceptibility to artifacts, high magnetic moment, dark signals, long processing time of T imaging, and long waiting time for patients after administration).

Tumor-Generated Reactive Oxygen Species Storm for High-Performance Ferroptosis Therapy.

Ferroptosis therapy (FT) efficacy of tumors suffers from a relatively low concentration of Fenton agents, limited hydrogen peroxide (HO) content, and insufficient acidity in the tumor environment (TME), which are unfavorable for reactive oxygen species (ROS) generation based on Fenton or Fenton-like reactions. The glutathione (GSH) overexpression in TME can scavenge ROS and abate the FT performance. In this study, a strategy of ROS storm generation specifically initiated by the TME and our developed nanoplatforms (TAF-HMON-CuP@PPDG) is proposed for high-performance FT of tumors.

Nanoparticle-Based MRI-Guided Tumor Microenvironment Heating via the Synergistic Effect of Ferroptosis and Inhibition of TGF-β Signaling.

Although induction of ferroptosis and inhibition of transforming growth factor-β (TGF-β) signaling are both effective ways to reform the tumor microenvironment (TME) and render low-immunogenic tumors responsive to immune checkpoint inhibitor therapy, dose-limiting side effects remain major obstacles hindering their clinical application. Herein, novel sorafenib and anti-TGF-β antibody loaded Fe O /Gd O hybrid nanoparticles with conjugation of arginine-glycine-aspartic dimer (FeGd-HN@Sorafenib@TGF-β-antibody@RGD2, FG-STR) are developed. Sorafenib significantly enhances FeGd-HN-triggered ferroptosis and improves maturation and phagocytosis of dendritic cells (DCs) by inducing damage-associated molecular patterns released from ferroptotic cancer cells, while the anti-TGF-β antibody further synergizes with enhanced ferroptosis to promote DC maturation and the recruitment of CD8 T cells, thus heating the TME.

A highly effective "naked eye" colorimetric and fluorimetric curcumin-based fluorescent sensor for specific and sensitive detection of HO and .

Hydrogen peroxide (HO) is involved in many important tasks in normal cell metabolism and signaling. However, abnormal levels of HO are associated with the occurrence of several diseases. Therefore, it is important to develop a new method for the detection of HO and .

A Strategy of Fenton Reaction Cycloacceleration for High-Performance Ferroptosis Therapy Initiated by Tumor Microenvironment Remodeling.

The emerging tumor ferroptosis therapy confronts impediments of the tumor microenvironment (TME) with weak intrinsic acidity, inadequate endogenous H O , and a powerful intracellular redox balance system that eliminates toxic reactive oxygen species (ROS). Herein, a strategy of Fenton reaction cycloacceleration initiated by remodeling the TME for magnetic resonance imaging (MRI)-guided high-performance ferroptosis therapy of tumors is proposed. The synthesized nanocomplex exhibits enhanced accumulation at carbonic anhydrase IX (CAIX)-positive tumors based on the CAIX-mediated active targeting, and increased acidification via the inhibition of CAIX by 4-(2-aminoethyl) benzene sulfonamide (ABS) (remodeling TME).

Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System.

The upregulation of dihydroorotate dehydrogenase (DHODH) redox systems inside tumor cells provides a powerful shelter against lipid peroxidation (LPO), impeding ferroptosis-induced antitumor responses. To solve this issue, we report a strategy to block redox systems and enhance ferroptotic cancer cell death based on a layered double hydroxide (LDH) nanoplatform (siR/IONs@LDH) co-loaded with ferroptosis agent iron oxide nanoparticles (IONs) and the DHODH inhibitor (siR). siR/IONs@LDH is able to simultaneously release IONs and siR in a pH-responsive manner, efficiently generate toxic reactive oxygen species (ROS) an Fe-mediated Fenton reaction, and synergistically induce cancer cell death upon the acceleration of LPO accumulation.