Biomolecular Corona of Gold Nanoparticles: The Urgent Need for Strong Roots to Grow Strong Branches.

Gold nanoparticles (GNPs) are largely employed in diagnostics/biosensors and are among the most investigated nanomaterials in biology/medicine. However, few GNP-based nanoformulations have received FDA approval to date, and promising in vitro studies have failed to translate to in vivo efficacy. One key factor is that biological fluids contain high concentrations of proteins, lipids, sugars, and metabolites, which can adsorb/interact with the GNP's surface, forming a layer called biomolecular corona (BMC). The BMC can mask prepared functionalities and target moieties, creating new surface chemistry and determining GNPs' biological fate. Here, the current knowledge is summarized on GNP-BMCs, analyzing the factors driving these interactions and the biological consequences. A partial fingerprint of GNP-BMC analyzing common patterns of composition in the literature is extrapolated. However, a red flag is also risen concerning the current lack of data availability and regulated form of knowledge on BMC. Nanomedicine is still in its infancy, and relying on recently developed analytical and informatic tools offers an unprecedented opportunity to make a leap forward. However, a restart through robust shared protocols and data sharing is necessary to obtain "stronger roots". This will create a path to exploiting BMC for human benefit, promoting the clinical translation of biomedical nanotools.

Hydrogen Promotes the Growth of Platinum Pyramidal Nanocrystals by Size-Dependent Symmetry Breaking.

The growth of pyramidal platinum nanocrystals is studied by a combination of synthesis/characterization experiments and density functional theory calculations. It is shown that the growth of pyramidal shapes is due to a peculiar type of symmetry breaking, which is caused by the adsorption of hydrogen on the growing nanocrystals. Specifically, the growth of pyramidal shapes is attributed to the size-dependent adsorption energies of hydrogen atoms on {100} facets, whose growth is hindered only if they are sufficiently large. The crucial role of hydrogen adsorption is further confirmed by the absence of pyramidal nanocrystals in experiments where the reduction process does not involve hydrogen.

Catalytic Bioswitch of Platinum Nanozymes: Mechanistic Insights of Reactive Oxygen Species Scavenging in the Neurovascular Unit.

Oxidative stress is known to be the cause of several neurovascular diseases, including neurodegenerative disorders, since the increase of reactive oxygen species (ROS) levels can lead to cellular damage, blood-brain barrier leaking, and inflammatory pathways. Herein, we demonstrate the therapeutic potential of 5 nm platinum nanoparticles (PtNPs) to effectively scavenge ROS in different cellular models of the neurovascular unit. We investigated the mechanism underlying the PtNP biological activities, analyzing the influence of the evolving biological environment during particle trafficking and disclosing a key role of the protein corona, which elicited an effective switch-off of the PtNP catalytic properties, promoting their selective in situ activity. Upon cellular internalization, the lysosomal environment switches on and boosts the enzyme-like activity of the PtNPs, acting as an intracellular "catalytic microreactor" exerting strong antioxidant functionalities. Significant ROS scavenging was observed in the neurovascular cellular models, with an interesting protective mechanism of the Pt-nanozymes along lysosomal-mitochondrial axes.

Nanozymes based on octahedral platinum nanocrystals with {111} surface facets: glucose oxidase mimicking activity in electrochemical sensors.

The ability of shape-controlled octahedral Pt nanoparticles to act as nanozyme mimicking glucose oxidase enzyme is reported. Extended {111} particle surface facets coupled with a size comparable to natural enzymes and easy-to-remove citrate coating give high affinity for glucose, comparable to the enzyme as proven by the steady-state kinetics of glucose electrooxidation. The easy and thorough removal of the citrate coating, demonstrated by X-ray photoelectron spectroscopy analysis, allows a highly stable deposition of the nanozymes on the electrode. The glucose electrochemical detection (at -0.2 V vs SCE) shows a linear response between 0.36 and 17 mM with a limit of detection of 110 µM. A good reproducibility has been achieved, with an average relative standard deviation (RSD) value of 9.1% (n = 3). Similarly, a low intra-sensor variability has been observed, with a RSD of 6.6% (n = 3). Moreover, the sensor shows a long-term stability with reproducible performances for at least 2 months (RSD: 7.8%). Tests in saliva samples show the applicability of Pt nanozymes to commercial systems for non-invasive monitoring of hyperglycemia in saliva, with recoveries ranging from 92 to 98%.

Platinum Nanozyme-Enabled Colorimetric Determination of Total Antioxidant Level in Saliva.

Redox imbalance and oxidative stress-related biomarkers are raising increasing consensus in the scientific community for their significant role in a wide range of human disorders. In this framework, the total antioxidant capacity (TAC), namely, the overall pattern of both enzymatic and nonenzymatic antioxidant compounds within the body, represents an important bioanalytical parameter. To date, however, antioxidant assays require costly instrumentations, laboratory setups, and reagents, and they are invasive. Yet, their accuracy typically suffers from strong sensitivity to interfering matrices and inability to detect the complete pattern of physiological antioxidant molecules, due to the use of reaction schemes and probes/substrates that are not sensitive to the diverse range of relevant target species. Here, we exploit the enzyme-mimetic properties of platinum nanoparticles combined with hydroxyl radical probes produced at the particle surface to develop an effective detection scheme that is sensitive to both single electron transfer (SET) and hydrogen atom transfer (HAT) reactions, thus covering all the physiologically relevant antioxidant species. Importantly, the nanozyme-enabled method allows fast (5 min), accurate, and noninvasive evaluation of the body TAC through saliva via simple naked-eye or smartphone-based inspection.

Delivery of biologically active miR-34a in normal and cancer mammary epithelial cells by synthetic nanoparticles.

Functional RNAs, such as microRNAs, are emerging as innovative tools in the treatment of aggressive and incurable cancers. In this study, we explore the potential of silica dioxide nanoparticles (SiO2NPs) in the delivery of biologically active miRNAs. Focusing on the tumor-suppressor miR-34a, we evaluated miRNAs delivery by SiO2NPs into the mammary gland, using in vitro as well as in vivo model systems. We showed that silica nanoparticles can efficiently deliver miR-34a into normal and cancer epithelial cells grown in culture without major signs of toxicity. Delivered miRNA retained the ability to silence artificial as well endogenous targets and can reduce the growth of mammospheres in 3D culture. Finally, miR-34a delivery through intra-tumor administration of SiO2NPs leads to a reduced mammary tumor growth. In conclusion, our studies suggest that silica nanoparticles can mediate the delivery of miR-34a directly into mammary tumors while preserving its molecular and biological activity.

Nanocatalyst/Nanoplasmon-Enabled Detection of Organic Mercury: A One-Minute Visual Test.

We present a fast and sensitive nanosensor that can detect organic mercury, exploiting the combination of the catalytic and plasmonic properties of gold nanoparticles (AuNPs). The method is one-step and completely instrument-free, and has a colorimetric readout clearly detectable by simple visual inspection. The AuNPs catalyze efficient organic mercury reduction to the metallic form (Hg0 ), allowing its nucleation and amalgam formation on particle surface, with consequent aggregation-induced plasmon shift. This leads to very rapid (1 min) and specific colorimetric detection of mercury species. The achieved limit of detection (20 ppb) is compliant with current regulatory limits in food.

Biotransformation and Biological Interaction of Graphene and Graphene Oxide during Simulated Oral Ingestion.

The biotransformation and biological impact of few layer graphene (FLG) and graphene oxide (GO) are studied, following ingestion as exposure route. An in vitro digestion assay based on a standardized operating procedure (SOP) is exploited. The assay simulates the human ingestion of nanomaterials during their dynamic passage through the different environments of the gastrointestinal tract (salivary, gastric, intestinal). Physical-chemical changes of FLG and GO during digestion are assessed by Raman spectroscopy. Moreover, the effect of chronic exposure to digested nanomaterials on integrity and functionality of an in vitro model of intestinal barrier is also determined according to a second SOP. These results show a modulation of the aggregation state of FLG and GO nanoflakes after experiencing the complex environments of the different digestive compartments. In particular, chemical doping effects are observed due to FLG and GO interaction with digestive juice components. No structural changes/degradation of the nanomaterials are detected, suggesting that they are biopersistent when administered by oral route. Chronic exposure to digested graphene does not affect intestinal barrier integrity and is not associated with inflammation and cytotoxicity, though possible long-term adverse effects cannot be ruled out.

Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles.

Targeted delivery of anticancer drugs with nanocarriers can reduce side effects and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional tumor vessels limit the transport of the payload into solid tumors. The use of tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects. A peptide containing a tissue-penetrating (TP) consensus motif, capable of recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide (pep) previously developed. Neuroblastoma cell lines and cells derived from both xenografts and high-risk neuroblastoma patients show overexpression of neuropilin-1. In vitro studies reveal that TP-pep binds cell lines and cells derived from neuroblastoma patients more efficiently than pep. TP-pep, after coupling to doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to selective increase of vascular permeability in tumor tissues. Compared to pep-SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma activity in three neuroblastoma animal models mimicking the growth of neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep-targeted nanoparticles may represent an innovative strategy for neuroblastoma.

Relevance to investigate different stages of pregnancy to highlight toxic effects of nanoparticles: The example of silica.

Amorphous silica nanoparticles (SiO2NPs) have been recognized as safe nanomaterial, hence their use in biomedical applications has been explored. Data, however, suggest potential toxicity of SiO2 NPs in pregnant individuals. However, no studies relating nanoparticle biokinetic/toxicity to the different gestational stages are currently available. In this respect, we have investigated the possible embryotoxic effects of three-size and two-surface functionalization SiO2NPs in mice. After intravenous administration of different concentrations at different stages of pregnancy, clinical and histopathological evaluations, performed close to parturition, did not show signs of maternal toxicity, nor effects on placental/fetal development, except for amino-functionalized 25 nm NPs. Biodistribution was studied by ICP-AES 24 h after administration, and demonstrates that all particles distributed to placenta and conceptuses/fetuses, although size, surface charge and gestational stage influenced biodistribution. Our data suggest the need of comprehensive toxicological studies, covering the entire gestation to reliably assess the safety of nanoparticle exposure during pregnancy.