Quantum Dots

Cuproptosis that utilizes copper ionophore to induce programmed cell death holds promise for enhancing the effectiveness of conventional anticancer therapies and triggering efficient adaptive immune responses. However, the non-tumor-specific release of Cu ions can induce cuproptosis and cause irreversible damage to normal tissues. To maximize the therapeutic effects of tumor-specific cuproptosis, this work reports for the first time the regulation of degradation behaviors of Cu-based nanomaterials using graphene quantum dots (GQDs) as a protection layer. The deposition of GQDs not only avoids the degradation of Cu2O nanocubes under normal physiological conditions, but also sensitizes their sonodynamic activity due to the formation of Z-scheme heterojunctions. The tumor-specific released Cu ions achieve the cascade amplification of reactive oxygen species (ROS) generation through Cu+-mediated Fenton-like reaction and Cu2+-facilitated GSH depletion. More importantly, the immunosuppressive tumor microenvironment (TME) can be reversed by the greatly enhanced ROS levels and high-efficiency cuproptosis, ultimately inducing immunogenic cell death that promotes robust systemic immune responses for the eradication of primary tumors and suppression of distant tumors. This work provides a novel paradigm for the integration of SDT, CDT, cuproptosis, and immunotherapy in a controlled manner to achieve tumor-specific antitumor therapy by controlling the degradation behaviors of Cu-based nanomaterials.

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.

Carbon quantum dots (CQDs), a new class of carbon-based nanomaterials, have emerged as nano-scaled probes with photoluminescence that have an eco-friendly and bio-compatible nature. Their cost-efficient synthesis and high photoluminescence quantum yields make them indispensable due to their application in opto-electronic devices, including biosensors, bioimaging, environmental monitoring, and light sources. This review provides intrinsic properties of CQDs such as their excitation-dependent emission, biocompatibility, and quenching properties. Diverse strategies for their easy synthesis are divided into bottom-up and top-down approaches and detailed herein. In particular, we highlight their luminescence properties, including quenching mechanisms that could even be utilized for the precise and rapid detection of biomolecules. We also discuss methodologies for the mitigation of fluorescence quenching, which is pivotal for the application of CQDs in biosensors and bioimaging.

IntroductionThe accumulation of reactive oxygen species (ROS) in diabetic wounds leads to inflammation and impaired neovascularization. Recent studies have indicated that carbon dot nanozymes (C-dots) exhibiting superoxide dismutase (SOD)-like activity can neutralize excessive ROS and mitigate diseases associated with oxidative stress.ObjectivesOur study was designed to evaluate the therapeutic impact of C-dots on the healing of diabetic wounds and to unravel the complex molecular mechanisms through which these nanozymes modulate oxidative stress and inflammatory responses within the wound microenvironment.Methods and resultsWe synthesized C-dots from carbon fiber and confirmed their structure using transmission electron microscopy. The presence of carbon-carbon double bonds on the C-dots was verified with X-ray photoelectron spectroscopy. We assessed the scavenging capacity of C-dots for superoxide anion, hydroxyl radical, and nitric oxide radical using electron spin resonance spectroscopy. Their SOD-like activity and total antioxidant capacity were evaluated with commercial assay kits. In vitro experiments showed that C-dots effectively scavenged excessive ROS, protecting human keratinocytes, vascular endothelial cells, and fibroblasts from oxidative stress-induced damage. Concurrently, C-dots increased the migratory capacity of fibroblasts. In a streptozocin-induced diabetic mice model, C-dots application enhanced skin wound healing, evidenced by accelerated re-epithelialization and orderly collagen matrix assembly. Mechanistic investigations indicated that C-dots markedly suppressed ROS generation and diminished the levels of inflammatory cytokines in the wound environment. Additionally, C-dots induced an M2 polarization phenotype in macrophages and promoted neovascularization, indicating a transition from the inflammatory to the proliferative phase. Quantitative proteomic analysis was conducted to further clarify the underlying mechanisms of C-dots in ameliorating diabetic wounds.ConclusionC-dots represent a robust nanomaterial-based strategy for treating diabetic wounds, with the ability to accelerate healing by alleviating oxidative stress, mitigating harmful inflammatory responses, and fostering angiogenesis. This highlights their significant therapeutic potential in the field of biomedicine.