The rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O2 and H2O2 to superoxide anion free radical (•O2-) and hydroxyl radical (•OH), which possess an excellent bactericidal effect. Also, the glutathione peroxidase (GPX)-like activity of Fe SAzymes can consume glutathione in the infection microenvironment, thus facilitating ROS generation to enhance the sterilization effect. Besides, the intrinsic photothermal effect of Fe SAzymes further significantly boosts the enzyme-like activity to generate much more reactive oxygen species for efficient antibacterial therapy. Accordingly, both in vitro and in vivo results indicate that the Fe SAzymes with synergistically photothermal-catalytic performances exhibit satisfactory antibacterial effects and biocompatibility. This work provides new insights into designing highly efficient SAzymes for effective sterilization applications by an amount of ROS generation.
Photothermal therapy (PTT) offers a promising approach for the treatment of drug-resistant bacterial-infected wounds, yet it requires precise targeting of thermal damage to bacteria rather than healthy tissues. Herein, ultrasmall CuS NPs modified with polyzwitterion containing acylsulfonamide betaine (PCBSA@CuS), which provides a sensitive and reversible charge conversion around pH 6.8, are used to enhance the healing of bacteria-infected wounds. In the acidic infection microenvironment, the majority of PCBSA@CuS can electrostatically adsorb onto bacterial cells through cationic exposure, resulting in direct damage and death of bacteria upon NIR irradiation. Additionally, the photothermal NPs rapidly return to a zwitterionic nature in normal physiological environments, ensuring lower affinity and avoiding thermal damage to healthy tissues during continuous PTT. Compared to inert photothermal systems such as PEG-modified CuS NPs, the NPs used in this study exhibited higher bactericidal and wound healing efficacy. Therefore, this nano-antibacterial agent with highly sensitive thermal-targeting function provides a novel photothermal strategy for efficient and biosafe treatment of infected wounds.
Carbon dots (CDs), as an emerging nanomaterial, have shown tremendous potential in disease biomarker detection. CDs can selectively interact with different target molecules, enabling highly sensitive and specific detection of these biomolecules. Compared to traditional detection methods, CDs sensors offer advantages such as rapid response, high detection sensitivity, and low cost. In this review, we summarize the latest advances in the application of CDs fluorescence probes for the detection of disease biomarkers, including sensing mechanisms, and their applications in the selective detection of metal ions, amino acids, enzymes, proteins, other biomolecules, as well as bacteria and viruses. We discuss the current challenges and issues associated with the practical application of CDs-based fluorescent probes. Furthermore, we propose future directions for the development of CDs. We hope that this review will provide new insights for researchers in the field of disease biomarker detection.
Multidrug resistance (MDR) is an incidental trouble post-chemotherapy, necessitating innovative therapeutic strategies. This study explores the potential of chloroquine (CQ) as a sensitizer for mitoxantrone hydrochloride (MitH) in drug-resistant tumors and introduces a novel pH-responsive drug-induced self-assembly nanovesicle (DIV) based on an amphiphilic polyphosphonitrile (PPAP) for the co-delivery of MitH and CQ. PPAP cannot self-assemble into nanovesicles alone, but when a certain amount of MitH was added, the multiple non-covalent interactions between PPAP and MitH contributed to the formation of DIV, which exactly improved the co-loading content of MitH and CQ to a large extent. CQ prevents MitH efflux and autophagy to reverse MitH resistance. Given the synergy between MitH and CQ at a 1:2 mass ratio with a combination index of 0.40 in K562/ADR cells, MitH and CQ co-loaded DIV (MC-DIV) is constructed and demonstrates a sensitivity index of 7.1 on cytotoxicity compared to free MitH. Furthermore, MC-DIV achieves extended circulation time, synchronous dual-drug delivery, and improved tumor targeting following systemic administration, resulting in exceptional antitumor efficacy in K562/ADR xenograft models with a tumor inhibition rate of 83.0 %. Overall, MC-DIV provides a viable method to maximize the loading capacity of nanocarriers, and potentially serves as a promising formulation for various MitH-resistant tumors.
Ferroptosis, which depends on iron ions to generate reactive oxygen species (ROS), has been proved to be an effective strategy for cancer therapy. However, cells will initiate different programs, including reducing iron uptake and storing excess iron in ferritin, to lower the intracellular iron concentration. In this work, we reported a simple, one-pot method to synthesize bovine serum albumin stabilized MnFe2O4 nanoparticles (MnFe2O4@BSA NPs) for ferroptosis therapy of cancer. Artemisinin (ART) and salinomycin (Sali), which could induce the degradation of ferritin and enhance the uptake by increasing binding protein IRP2 and transferrin receptor, were loaded onto the MnFe2O4@BSA NPs to strengthen the killing effect. The prepared MnFe2O4@BSA-ART/Sali (MnFe2O4/ART/Sali) NPs could significantly increase the cellular iron concertation, enhancing the ROS generation in cells. After intravenous injection, the MnFe2O4/ART/Sali NPs showed superior anti-tumor effects, with a tumor inhibition rate of 67.65 %. Hence, the hybrid nanocomposite indicated the combined effect of MnFe2O4, ART, and Sali, providing a platform to enhance ferroptosis therapy of cancer.