Small Warriors of Nature: Novel Red Emissive Chlorophyllin Carbon Dots Harnessing Fenton-Fueled Ferroptosis for In Vitro and In Vivo Cancer Treatment.

The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.

Synergized photothermal therapy and magnetic field induced hyperthermia via bismuthene for lung cancer combinatorial treatment.

Thanks to its intrinsic properties, two-dimensional (2D) bismuth (bismuthene) can serve as a multimodal nanotherapeutic agent for lung cancer acting through multiple mechanisms, including photothermal therapy (PTT), magnetic field-induced hyperthermia (MH), immunogenic cell death (ICD), and ferroptosis. To investigate this possibility, we synthesized bismuthene from the exfoliation of 3D layered bismuth, prepared through a facile method that we developed involving surfactant-assisted chemical reduction, with a specific focus on improving its magnetic properties. The bismuthene nanosheets showed high in vitro and in vivo anti-cancer activity after simultaneous light and magnetic field exposure in lung adenocarcinoma cells. Only when light and magnetic field are applied together, we can achieve the highest anti-cancer activity compared to the single treatment groups. We have further shown that ICD-dependent mechanisms were involved during this combinatorial treatment strategy. Beyond ICD, bismuthene-based PTT and MH also resulted in an increase in ferroptosis mechanisms both in vitro and in vivo, in addition to apoptotic pathways. Finally, hemolysis in human whole blood and a wide variety of assays in human peripheral blood mononuclear cells indicated that the bismuthene nanosheets were biocompatible and did not alter immune function. These results showed that bismuthene has the potential to serve as a biocompatible platform that can arm multiple therapeutic approaches against lung cancer.

Low Dose of Ti3 C2 MXene Quantum Dots Mitigate SARS-CoV-2 Infection.

MXene QDs (MQDs) have been effectively used in several fields of biomedical research. Considering the role of hyperactivation of immune system in infectious diseases, especially in COVID-19, MQDs stand as a potential candidate as a nanotherapeutic against viral infections. However, the efficacy of MQDs against SARS-CoV-2 infection has not been tested yet. In this study, Ti3 C2 MQDs are synthesized and their potential in mitigating SARS-CoV-2 infection is investigated.  Physicochemical characterization suggests that MQDs are enriched with abundance of bioactive functional groups such as oxygen, hydrogen, fluorine, and chlorine groups as well as surface titanium oxides. The efficacy of MQDs is tested in VeroE6 cells infected with SARS-CoV-2. These data demonstrate that the treatment with MQDs is able to mitigate multiplication of virus particles, only at very low doses such as 0,15 µg mL-1 . Furthermore, to understand the mechanisms of MQD-mediated anti-COVID properties, global proteomics analysis are performed and determined differentially expressed proteins between MQD-treated and untreated cells. Data reveal that MQDs interfere with the viral life cycle through different mechanisms including the Ca2 + signaling pathway, IFN-α response, virus internalization, replication, and translation. These findings suggest that MQDs can be employed to develop future immunoengineering-based nanotherapeutics strategies against SARS-CoV-2 and other viral infections.

2D Materials for Cardiac Tissue Repair and Regeneration.

Cardiovascular diseases (CVDs) have a massive impact on human health. Due to the limited regeneration capacity of adult heart tissue, CVDs are the leading cause of death and disability worldwide. Even though there are surgical and pharmacological treatments for CVDs, regenerative strategies are the most promising approaches and have the potential to benefit millions of people. As in any other tissue engineering approach, the repair and regeneration of damaged cardiac tissues generally involve scaffolds made up of biodegradable and biocompatible materials, cellular components such as stem cells, and growth factors. This review provides an overview of biomaterial-based tissue engineering approaches for CVDs with a specific focus on the potential of 2D materials. It is essential to consider both physicochemical and immunomodulatory properties for evaluating the applicability of 2D materials in cardiac tissue repair and regeneration. As new members of the 2D materials will be explored, they will quickly become part of cardiac tissue engineering technologies.

Emerging 2D materials for antimicrobial applications in the pre- and post-pandemic era.

Infectious diseases caused by viral or bacterial pathogens are one of the most serious threats to humanity. Moreover, they may lead to pandemics, as we have witnessed severely with the coronavirus disease 2019 (COVID-19). Nanotechnology, including technological developments of nano-sized materials, has brought great opportunities to control the spreading of such diseases. In the family of nano-sized materials, two-dimensional (2D) materials with intrinsic physicochemical properties can efficiently favor antimicrobial activity and maintain a safer environment to protect people against pathogens. For this purpose, they can be used alone or combined for the disinfection process of microbes, antiviral or antibacterial surface coatings, air filtering of medical equipment like face masks, or antimicrobial drug delivery systems. At the same time, they are promising candidates to deal with the issues of conventional antimicrobial approaches such as low efficacy and high cost. This review covers the antiviral or antibacterial activities of 2D materials and highlights their current and possible future applications. Considering their intrinsic properties, 2D materials will become part of the leading antimicrobial technologies for combating future pandemics anytime soon.

2D MXenes with antiviral and immunomodulatory properties: A pilot study against SARS-CoV-2.

Two-dimensional transition metal carbides/carbonitrides known as MXenes are rapidly growing as multimodal nanoplatforms in biomedicine. Here, taking SARS-CoV-2 as a model, we explored the antiviral properties and immune-profile of a large panel of four highly stable and well-characterized MXenes - Ti3C2Tx, Ta4C3T x , Mo2Ti2C3T x and Nb4C3T x . To start with antiviral assessment, we first selected and deeply analyzed four different SARS-CoV-2 genotypes, common in most countries and carrying the wild type or mutated spike protein. When inhibition of the viral infection was tested in vitro with four viral clades, Ti3C2T x in particular, was able to significantly reduce infection only in SARS-CoV-2/clade GR infected Vero E6 cells. This difference in the antiviral activity, among the four viral particles tested, highlights the importance of considering the viral genotypes and mutations while testing antiviral activity of potential drugs and nanomaterials. Among the other MXenes tested, Mo2Ti2C3T x also showed antiviral properties. Proteomic, functional annotation analysis and comparison to the already published SARS-CoV-2 protein interaction map revealed that MXene-treatment exerts specific inhibitory mechanisms. Envisaging future antiviral MXene-based drug nano-formulations and considering the central importance of the immune response to viral infections, the immune impact of MXenes was evaluated on human primary immune cells by flow cytometry and single-cell mass cytometry on 17 distinct immune subpopulations. Moreover, 40 secreted cytokines were analyzed by Luminex technology. MXene immune profiling revealed i) the excellent bio and immune compatibility of the material, as well as the ability of MXene ii) to inhibit monocytes and iii) to reduce the release of pro-inflammatory cytokines, suggesting an anti-inflammatory effect elicited by MXene. We here report a selection of MXenes and viral SARS-CoV-2 genotypes/mutations, a series of the computational, structural and molecular data depicting deeply the SARS-CoV-2 mechanism of inhibition, as well as high dimensional single-cell immune-MXene profiling. Taken together, our results provide a compendium of knowledge for new developments of MXene-based multi-functioning nanosystems as antivirals and immune-modulators.