Abstract Aggressive cancers, characterized by high metastatic potential and resistance to conventional therapies, present a significant challenge in oncology. Current treatments often fail to effectively target metastasis, recurrence, and the immunosuppressive tumor microenvironment, while causing significant off‐target toxicity. Here, superparamagnetic copper iron oxide nanoparticles (SCIONs) as a multifunctional platform that integrates magnetic hyperthermia therapy, immune modulation, and targeted chemotherapeutic delivery, aiming to provide a more comprehensive cancer treatment is presented. Specifically, SCIONs generate localized hyperthermia under an alternating magnetic field while delivering a copper‐based anticancer agent, resulting in a synergistic anticancer effect. The hyperthermia induced by SCIONs caused ER stress and ROS production, leading to significant tumor cell death, while the copper complex further enhanced oxidative stress, ferroptosis, and apoptosis. Beyond direct cytotoxicity, SCIONs disrupted the tumor microenvironment by inhibiting cancer‐associated fibroblasts, downregulating epithelial‐mesenchymal transition markers, and reducing cell migration and invasion, thereby limiting metastasis. Additionally, SCION‐based therapy reprogrammed the immune microenvironment by inducing immunogenic cell death and enhancing dendritic cell activation, resulting in increased CD8+ T cell infiltration and amplified antitumor immunity. This integrated approach targets primary and metastatic tumors while mitigating immunosuppression, offering a promising next‐generation therapy for combating cancer with enhanced efficacy and reduced side effects.
more »
« less
Operando investigation of the synergistic effect of electric field treatment and copper for bacteria inactivation
Abstract As the overuse of chemicals in our disinfection processes becomes an ever-growing concern, alternative approaches to reduce and replace the usage of chemicals is warranted. Electric field treatment has shown promising potential to have synergistic effects with standard chemical-based methods as they both target the cell membrane specifically. In this study, we use a lab-on-a-chip device to understand, observe, and quantify the synergistic effect between electric field treatment and copper inactivation. Observations in situ, and at a single cell level, ensure us that the combined approach has an enhancement effect leading more bacteria to be weakened by electric field treatment and susceptible to inactivation by copper ion permeation. The synergistic effects of electric field treatment and copper can be visually concluded here, enabling the further study of this technology to optimally develop, mature, and scale for its various applications in the future.
more »
« less
- Award ID(s):
- 1845354
- PAR ID:
- 10490822
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 15
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Contamination of high‐touch surfaces with infected droplets of bodily secretions is a known route of virus transmission. Copper surfaces have been reported to inactivate human coronaviruses after several minutes, via the release of Cu cations. Utilization of copper alloys for high‐touch surfaces can be a pivotal preemptive strategy for preventing the next pandemic. Understanding the true efficacy by which copper, and copper alloys, inactivate the virus under realistic conditions is essential for tuning intrinsic alloy features such as composition, grain orientation, and surface attributes, to optimize for antiviral function. However, virus inactivation measurements depend on the presence of an assay media (AM) solution as a carrier for the virus, and its effects on the surface properties of pure copper that regulate oxidative copper release are previously unknown. Herein, these properties and the influence of AM on the efficacy of virus inactivation occurring on the surface of pure copper are investigated. The process is uncovered by which a five‐fold decrease in virus half‐life is observed in simulated real‐life conditions, relative to exposure to traditional AM. The investigation highlights the notion that virus inactivation on copper surfaces may be significantly more effective than previously thought.more » « less
-
Legionella pneumophila is a virulent bacterial pathogen that can cause a severe and deadly form of pneumonia called Legionnaires’ disease. Risk of infection increases when L. pneumophila are harbored inside free-living amoebae, which are resistant to traditional disinfection processes but lyse upon heat exposure. This project aims to develop a point-of-use technology based on microwave (MW) radiation and nanomaterial (e.g., silver, copper oxide, carbon nanotubes) exposure for L. pneumophila control. In this alternative technology, we hypothesize that amoebae will be lysed via localized interfacial heating, and the released L. pneumophila will be inactivated subsequently by heat, metal ions (from nanoparticle dissolution), and reactive oxygen species (ROS) produced in the process. The synergistic effect of microwaves and silver nanoparticles for enhanced, rapid inactivation has been demonstrated for Escherichia coli and planktonic L. pneumophila. Inactivation greater than 3-logs of each species has been achieved when subjected to silver nanoparticles (2-5 mg/L) and MW (2,450 MHz; 70 W) radiation. A mechanistic study using E. coli has determined the dominant interaction to be between released ions and MW radiation. Ultimately, the nanomaterials will be immobilized on a plaster of Paris or ceramic surface for flow through applications where both amoeba lysing and L. pneumophila inactivation will be achieved.more » « less
-
Cao, Yi (Ed.)PEMF (Pulsed Electromagnetic Field) stimulation has been used for therapeutic purposes for over 50 years including in the treatment of memory loss, depression, alleviation of pain, bone and wound healing, and treatment of certain cancers. However, the underlying cellular mechanisms mediating these effects have remained poorly understood. In particular, because magnetic field pulses will induce electric currents in the stimulated tissue, it is unclear whether the observed effects are due to the magnetic or electric component of the stimulation. Recently, it has been shown that PEMFs stimulate the formation of ROS (reactive oxygen species) in human cell cultures by a mechanism that requires cryptochrome, a putative magnetosensor. Here we show by qPCR analysis of ROS-regulated gene expression that simply removing cell cultures from the Earth’s geomagnetic field by placing them in a Low-Level Field condition induces similar effects on ROS signaling as does exposure of cells to PEMF. This effect can be explained by the so-called Radical Pair mechanism, which provides a quantum physical means by which the rates and product yields (e.g. ROS) of biochemical redox reactions may be modulated by magnetic fields. Since transient cancelling of the Earth’s magnetic field can in principle be achieved by PEMF exposure, we propose that the therapeutic effects of PEMFs may be explained by the ensuing modulation of ROS synthesis. Our results could lead to significant improvements in the design and therapeutic applications of PEMF devices.more » « less
-
Chlorine disinfection inevitably generates carcinogenic by-products. Alternative non-chlorine-based techniques in centralized treatment plants cannot produce residual antimicrobial power in water disinfection systems. Here, we propose locally enhanced electric field treatment (LEEFT) for chemical-free water disinfection in pipes. A tubular LEEFT device with coaxial electrodes is rationally developed for easy adaption to current water distribution systems as a segment of the pipelines. The center electrode is modified with perpendicularly grown nanowires, so that the electric field strength near the tips of the nanowires is significantly enhanced for pathogen inactivation. We have demonstrated >6-log inactivation of bacteria with 1 V, a small voltage that can be generated in situ by flowing water.more » « less
An official website of the United States government
