The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.
Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol derivatisation with the phenyl boronic acid moiety at the meso position of the BODIPY core, allowed to preserve the intrinsic properties of GO. We demonstrated that both chlorine atoms were substituted by GSH in the presence of glutathione transferase (GST), inducing a relevant bathochromic shift in the absorption/emission features and thus generating the active PS. Ex vitro assessment using cell lysates containing cytoplasmatic GST revealed the intracellular catalytic mechanism for the nucleophilic substitution of the GO-BODIPY adduct with GSH. Confocal microscopy studies showed important differences in the cellular uptake of free BODIPY and GO-BODIPY and revealed the coexistence of GO-BODIPY, GO-BODIPY-GS, and GO-BODIPY-GS2 species inside vesicles and in the cytoplasm of the cells after 24 h of incubation. In vitro biocompatibility and safety of GO and GO-BODIPY were evaluated in 2D and 3D models of prostate adenocarcinoma cells (PC-3), where no toxicity was observed up to 100 µg/mL of GO/GO-BODIPY in all treated groups 24 h post-treatment (cell viability > 90%). Only a slight decrease to 80% at 100 µg/mL was observed after 48 h of incubation. We demonstrated the efficacy of a GO adduct containing an α-chlorine-substituted BODIPY for the simultaneous depletion of intracellular GSH and the photogeneration of reactive oxygen species using a halogen white light source (5.4 mW/cm2) with a maximum in the range of 500-800 nm, which significantly reduced cell viability (< 50%) after irradiation. Our study provides a new vision on how to apply BODIPY derivates and potentiate the toxicity of PDT in prostate and other types of cancer.
Carbon-based nanomaterials exist in different forms, and the key which links all these nanomaterials lies in the high percentage of carbon atoms connected through sp 2 or sp 3 bonds. The small size and the different properties of these materials stir a strong interest in different application fields from electronics to biomedicine. Especially, carbon-based nanomaterials have received a growing interest due to their interaction with light. [1] This property can be exploited in a wide variety of applications, including phototherapy. The therapeutic benefit of phototherapy lies on an easy and flexible control of the light irradiation, the possibility to treat specific localized areas, as well as control time and dose of the therapeutic action. [2] Depending on their interaction with light, two classes of phototherapies can operate. The first is the photothermal therapy (PTT), which consists of the conversion of the adsorbed light by a material into surface vibrations producing heat. The local increase of the temperature can induce photoablation of tumor cells. [3] The second is the photodynamic therapy (PDT), where the interaction with light produces free radicals and, most importantly, reactive oxygen species (ROS). This leads to high oxidative stress that destabilizes cell machinery and induces apoptosis. [4] PDT is currently the most explored type of phototherapy for cancer treatment. Compared to PTT, PDT was already approved by FDA. [5] Within the different classes of carbon materials, graphene family nanomaterials have gained a lot of consensuses as tools in cancer therapy. They are composed of hexagonal rings of carbon with electron delocalization depending on the type of graphene material. [6] These 2D materials are good photothermal agents due to their ability to absorb at near-infrared (NIR) wavelengths. [7] Graphene generally shows poor colloidal stability, and this limits its use in drug delivery. [8] Graphene oxide (GO) is the oxidized form of graphene. The oxidative synthesis process enriches GO surface with a wide variety of organic groups such as epoxides, hydroxyl and carboxyl groups. [8] Because of its biocompatibility, hydrophilicity, high colloidal stability, and versatile surface chemistry, the biomedical applications of GO have been widely explored. In addition, GO can be easily
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