다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Since the first connection between Fenton chemistry and biomedicine, numerous studies have been presented in this field. Comprehensive presentation of the guidance from Fenton chemistry and a summary of its representative applications in cancer therapy would help us understand and promote the further development of this field. This comprehensive review first supplies basic information regarding Fenton chemistry, including Fenton reactions and Fenton-like reactions. Subsequently, the current progress of Fenton chemistry is discussed, with some corresponding representative examples presented. Furthermore, the current strategies for further optimizing the performance of chemodynamic therapy guided by Fenton chemistry are highlighted. Most importantly, future perspectives on the combination of biomedicine with Fenton chemistry or a wider range of catalytic chemistry approaches are presented. We hope that this review will attract positive attention in the chemistry, materials science, and biomedicine fields and further tighten their connections.

Biomedicine Meets Fenton Chemistry.

Glutathione (GSH), the main redox buffer, has long been recognized as a pivotal modulator of tumor initiation, progression and metastasis. It is also implicated in the resistance of platinum-based chemotherapy and radiation therapy. Therefore, depleting intracellular GSH was considered a potent solution to combating cancer. However, reducing GSH within cancer cells alone always failed to yield desirable therapeutic effects. In this regard, the convergence of GSH-scavenging agents with therapeutic drugs has thus been pursued in clinical practice. Unfortunately, the therapeutic outcomes are still unsatisfactory due to untargeted drug delivery. Advanced nanomedicine of synergistic GSH depletion and cancer treatment has attracted tremendous interest because they promise to deliver superior therapeutic benefits while alleviating life-threatening side effects. In the past five years, the authors and others have demonstrated that numerous nanomedicines, by simultaneously delivering GSH-depleting agents and therapeutic components, boost not only traditional chemotherapy and radiotherapy but also multifarious emerging treatment modalities, including photodynamic therapy, sonodynamic therapy, chemodynamic therapy, ferroptosis, and immunotherapy, to name a few, and achieved decent treatment outcomes in a large number of rodent tumor models. In this review, we summarize the most recent progress in engineering nanomedicine for GSH depletion-enhanced cancer therapies. Biosynthesis of GSH and various types of GSH-consuming strategies will be briefly introduced. The challenges and perspectives of leveraging nanomedicine for GSH consumption-augmented cancer therapies will be discussed at the end.

Engineering nanomedicine for glutathione depletion-augmented cancer therapy

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism. Furthermore, dysregulation of mitochondrial metabolism is considered a biochemical feature of neurodegenerative diseases linked to ferroptosis. Whether mitochondrial dysfunction can, per se, initiate ferroptosis and whether mitochondrial function in ferroptosis is context-dependent are still under debate. Cancer cells accumulate high levels of iron and ROS to promote their metabolic activity and growth. Of note, cancer cell metabolic rewiring is often associated with acquired sensitivity to ferroptosis. This strongly suggests that ferroptosis may act as an adaptive response to metabolic imbalance and, thus, may constitute a new promising way to eradicate malignant cells. Here, we review the current literature on the role of mitochondria in ferroptosis, and we discuss opportunities to potentially use mitochondria-mediated ferroptosis as a new strategy for cancer therapy.

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure-property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.

Glutathione-Depleting Nanomedicines for Synergistic Cancer Therapy.

Triggered ferroptotic polymer micelles for reversing multidrug resistance to chemotherapy

Ferroptosis is an iron-dependent cell death pathway that can eradicate certain apoptosis-insensitive cancer cells. The ferroptosis-inducing molecules are tailored lipid peroxides whose efficacy is compromised in hypoxic solid tumor and lack of tumor selectivity. It has been demonstrated that ascorbate (Asc) in pharmacological concentrations can selectively kill cancer cells via accumulating hydrogen peroxide (H2O2) only in tumor extracellular fluids. It was hypothesized that Asc-induced, selective enrichment of H2O2 in tumor coupled with Fe3+ codelivery could simultaneously address the above two problems via boosting the levels of hydroxyl radicals and oxygen in the tumor site to ease peroxidation initiation and propagation, respectively. The aim of this work was to synergize the action of Asc with lipid-coated calcium phosphate (CaP) hybrid nanocarrier that can concurrently load polar Fe3+ and nonpolar RSL3, a ferroptosis inducer with the mechanism of inhibiting lipid peroxide repair enzyme (GPX4). The hybrid nanocarriers showed accelerated cargo release at acidic conditions (pH 5.0). The combinational approach (Asc plus nanocarrier) produced significantly elevated levels of hydroxyl radicals, lipid peroxides, and depleted glutathione under hypoxia, which was accompanied with the strong cytotoxicity (IC50 = 1.2 ± 0.2 μM) in the model 4 T1 cells. In the 4 T1 tumor-bearing xenograft mouse model, the intravenous nanocarrier delivery plus intraperitoneal Asc administration resulted in a superior antitumor performance in terms of tumor suppression, which did not produce supplementary adverse effects to the healthy organs. This work provides a novel approach to enhance the potency of ferroptotic nanomedicine against solid tumors without inducing additional side effects.

Boosting the Ferroptotic Antitumor Efficacy via Site-Specific Amplification of Tailored Lipid Peroxidation.

Boosting output charge density is top priority for achieving high‐performance triboelectric nanogenerators (TENGs). The charge‐excitation strategy is demonstrated to be a superior approach to acquire high output charge density. Meanwhile, the molecular charge behaviors in the dielectric under a strong electric field from high charge density bring new physics that are worth exploring. Here, a rapid self‐polarization effect of a polar dielectric material by the superhigh electric field in a charge‐excitation TENG is reported, by which the permittivity of the polar dielectric material realizes self‐increase to a saturation, and thus enhances the output charge density. Consequently, an ultrahigh charge density of 3.53 mC m−2 is obtained with 7 µm homemade lead zirconate titanate−poly(vinylidene fluoride) composite film in the atmosphere with 5% relative humidity, which is the highest charge density for TENGs with high durability currently. This work provides new guidance for dielectric material optimization under charge excitation to boost the output performance of TENGs toward practical applications.

Achieving Remarkable Charge Density via Self‐Polarization of Polar High‐k Material in a Charge‐Excitation Triboelectric Nanogenerator

Triboelectric nanogenerators (TENGs) are regarded as a promising technology to convert ambient low‐frequency mechanical energy into electricity for distributed power supply. Although TENGs based on triboelectrification (TE) of metal–dielectric and air breakdown have the advantage of direct current (DC) output, the unidirectional and single‐channel output mode limits their energy utilization efficiency. Here, a bidirectional and double‐channel (BDC‐TENG) based on TE of dielectric–dielectric and local corona discharge is proposed. Different from traditional DC‐TENGs, the TE process of the BDC‐TENG occurs in two dielectrics, and the double‐channel output is generated from simultaneous discharge between each dielectric and its adjacent electrode fixed on both sides of the slider. The BDC‐TENG shows unique characteristics, in that the current direction is tunable by adjusting the slider movement direction and electronegativity difference of two dielectric materials, and the average output power density is up to 3 W m–2 which is 14 times higher than that of traditional DC‐TENGs. This work provides a feasible strategy to boost the output performance of DC‐TENGs.

A High‐Performance Bidirectional Direct Current TENG by Triboelectrification of Two Dielectrics and Local Corona Discharge

Although charge excitation is an effective approach to achieve high charge density for triboelectric nanogenerators (TENGs), high output charge is limited by air‐breakdown. Due to capacitor structure, there are two ways to reduce the influence of air‐breakdown in TENG: decrease in thickness and increase in permittivity of dielectric film. Obviously, the increase in permittivity is more reliable in applications. Herein, a double‐layer TENG shared with one floating metal electrode is proposed, on which charge is injected by a self‐excitation circuit. An ultrafast self‐polarization effect is found in two barium titanate filled poly(vinylidene fluoride) composite films in the TENG by high electrical field produced from the floating electrode. According to comparison and analysis, the speed of polarization to saturation of dielectric composite films in self‐charge excitation approach is ≈3 times faster than that of external‐charge excitation. Optimization of various parameters is investigated to enhance the output performance of the TENG. A large output charge density of 1.67 mC m–2 is achieved in the atmosphere with 40% relative humidity due to self‐polarization effect of the dielectric composite film. This study provides insights into understanding the polarized behavior of molecules in dielectrics and further optimizing the output performance of TENGs in self‐charge excitation systems.

An Ultrafast Self‐Polarization Effect in Barium Titanate Filled Poly(Vinylidene Fluoride) Composite Film Enabled by Self‐Charge Excitation Triboelectric Nanogenerator

Huiyuan Wu

Papers

Triggered ferroptotic polymer micelles for reversing multidrug resistance to chemotherapy

Boosting the Ferroptotic Antitumor Efficacy via Site-Specific Amplification of Tailored Lipid Peroxidation.

Achieving Remarkable Charge Density via Self‐Polarization of Polar High‐k Material in a Charge‐Excitation Triboelectric Nanogenerator

A High‐Performance Bidirectional Direct Current TENG by Triboelectrification of Two Dielectrics and Local Corona Discharge

An Ultrafast Self‐Polarization Effect in Barium Titanate Filled Poly(Vinylidene Fluoride) Composite Film Enabled by Self‐Charge Excitation Triboelectric Nanogenerator