Effect of protein corona magnetite nanoparticles derived from bread in vitro digestion on Caco-2 cells morphology and uptake

Nanoparticles (NPs) in biological fluids immediately interact with proteins forming a biomolecular corona (PC) that imparts their biological identity. While several studies on the formation of the PC in human plasma have been reported, the PC of orally administrated NPs has been less investigated, mostly in the presence of a food matrix. In fact, food matrixes when digested are subject of several dynamic changes that will certainly affect the PC formed on the NPs. The lack of studies on this topic is clearly related to the difficulty in isolating representative PC NPs from such a complex environment. In this work magnetite NPs were added to in vitro simulated digestion simultaneously with bread and PC NPs were isolated after gastric and duodenal phases by sucrose gradient ultracentrifugation (UC). The PC NPs were characterized in terms of size and protein composition. Translocation studies were then performed on Caco-2 monolayers in a serum free environment and cell morphology was characterized by confocal microscopy. PC NPs isolated from gastric and duodenal phases were different in size, surface charge and protein corona composition. NP cellular uptake was enhanced by the digestive PC inducing morphology changes in the cell monolayer. Overall, in this work we were able to isolate PC NPs from digested fluids in the presence of a food matrix and study their biological response on Caco-2 cells.     

In-vitro in-vivo correlation (IVIVC) in nanomedicine: Is protein corona the missing link?

One of the unmet challenges in nanotechnology is to understand and establish the relationship between physicochemical properties of nanoparticles (NPs) and its biological interactions (bio-nano interactions). However, we are still far from assessing the biofate of NPs in a clear and unquestionable manner. Recent developments in the area of bio-nano interface and the understanding of protein corona (PC) has brought new insight in predicting biological interactions of NPs. PC refers to the spontaneous formation of an adsorbed layer of biomolecules on the surface of NPs in a biological environment. PC formation involves the spatiotemporal interplay of an intricate network of biological, environmental and particle characteristics. NPs with its PC can be viewed as a biological entity, which interacts with cells and barriers in a biological system. Recent studies on the bio-nano interface have revealed biological signatures that participate in cellular and physiological bioprocesses and control the biofate and toxicity of NPs. The ability of in-vitro derived parameters to forecast in-vivo consequences by developing a mathematical model forms the basis of in-vitro in-vivo correlation (IVIVC). Understanding the effect of bio-nano interactions on the biological consequences of NPs at the cellular and physiological level can have a direct impact on the translation of future nanomedicines and can lead to the ultimate goal of developing a mathematical IVIVC model. The review summarizes the emerging paradigms in the field of bio-nano-interface which clearly suggests an urgent need to revisit existing protocols in nanotechnology for defining the physicochemical correlates of bio-nano interactions.     

Nanoparticle-biomolecular corona: A new approach for the early detection of non-small-cell lung cancer

Lung cancer (LC) is the most common type of cancer and the second cause of death worldwide in men and women after cardiovascular diseases. Non-small-cell lung cancer (NSCLC) is the most frequent type of LC occurring in 85% of cases. Developing new methods for early detection of NSCLC could substantially increase the chances of survival and, therefore, is an urgent task for current research. Nowadays, explosion in nanotechnology offers unprecedented opportunities for therapeutics and diagnosis applications. In this context, exploiting the bio-nano-interactions between nanoparticles (NPs) and biological fluids is an emerging field of research. Upon contact with biofluids, NPs are covered by a biomolecular coating referred to as “biomolecular corona” (BC). In this study, we exploited BC for discriminating between NSCLC patients and healthy volunteers. Blood samples from 10 NSCLC patients and 5 subjects without malignancy were allowed to interact with negatively charged lipid NPs, leading to the formation of a BC at the NP surface. After isolation, BCs were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We found that the BCs of NSCLC patients was significantly different from that of healthy individuals. Statistical analysis of SDS-PAGE results allowed discriminating between NSCLC cancer patients and healthy subjects with 80% specificity, 80% sensitivity and a total discriminate correctness rate of 80%. While the results of the present investigation cannot be conclusive due to the small size of the data set, we have shown that exploitation of the BC is a promising approach for the early diagnosis of NSCLC.     

A health concern regarding the protein corona,aggregation and disaggregation

Nanoparticle (NP)–protein complexes exhibit the “correct identity” of NP in biological media. Therefore, protein–NP interactions should be closely explored to understand and modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, morphology of NPs, and influence of pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of techniques. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH, and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP–protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in vivo.     

Advances and potential application of gold nanoparticles in nanomedicine

Nanomedicine is an emerging research area which has brought new possibilities and promising applications in image, diagnosis, and treatment. Nanoparticles (NPs) for medicinal purposes can be made of several material types such as silica, carbon, different polymers, and metals as silver, copper, titanium, and gold. Gold NPs (AuNPs) are the most studied and used, mostly due to their characteristics including simple preparation, controllable size and distribution, biocompatibility, good acceptance of surface modifications, and specific surface plasmon resonance (SPR). This study reviews the scientific literature regarding the potential applications of AuNPs in the development of new diagnostic and therapeutic strategies for nanomedicine, including their biomedical use as a drug carrier, as an agent in radio and phototherapy, and bioimaging for image diagnosis. While it becomes clear that much research remains to be done to improve the use of these nanoparticles, with particular concern for safety issues, the evidence from the literature already points to the great potential of AuNPs in nanomedicine.     

Microscopic and spectroscopic study of the corona formation and unfolding of human haemoglobin in presence of ZnO nanoparticles

The interaction of zinc oxide nanoparticles (ZnO NPs) with human haemoglobin (Hb) is studied for the biologically safe application of ZnO NPs in the human body. The Hb corona is formed around the ZnO nanoparticles, directly observed from high‐resolution transmission electron microscopy (HRTEM) images. Hb formed ‘hard corona' on the surface of ZnO NPs from an exponential association mechanism over a very short duration, as well as unfolding of Hb that occurred over a long lifetime. Dynamic light scattering measurements demonstrated that the ZnO NPs were completely covered by Hb with shell thickness of c. 6 nm that formed a ‘hard corona'. Zeta potential measurements represented that the ZnO NPs were fully covered by Hb molecules using an exponential association mechanism. Tryptophans (TRY), as well as heme‐porphyrin moieties of Hb, are the major binding sites for ZnO NPs. The nature of the interaction between ZnO NPs and Hb was analysed from the fluorescence quenching of TRYs. Electrostatic interaction, along with the hydrophobic interaction between ZnO NPs and Hb, is responsible for the conformational change in Hb due to increase in the percentage of β‐sheets together with a decrease in α‐helices.     

Seaweeds: A resource for marine bionanotechnology

Marine bionanotechnology is one of the most promising areas of research in modern science and technology. Although there are multitude methods for the synthesis of nanoparticles (NPs), there is an increasing attention in developing high-yield, low-cost, non-toxic and eco-friendly procedures. The vital advantages of greener synthesis are cost-effective, reduced usage of toxic chemicals and abundant availability of resources. During the last ten years, there have been many biological entities used to elevate novel, greener and affordable methods for the metal NPs synthesis. Rate of synthesis and stability are higher for plant material mediated NPs. However, in comparison with terrestrial resources, marine resources have not been fully explored for synthesis of noble metal NPs. Our present review is designed to speculate the importance of usage of vast marine resources and its mediated NPs synthesis, in particular seaweed-mediated NPs synthesis to overcome the limitations involved in physical and chemical methods. Finally, recent advancements in greener synthesis of metal NPs, their size, distribution, morphology and applications such as antimicrobial, antifouling and anticancer potentials are briefly described along with portraying the prospective scope of research in this field without any negative impact on the environment.     

The importance of selecting a proper biological milieu for protein corona analysis in vitro: Human plasma versus human serum

Nanoparticle (NP) exposure to biological fluids in the body results in protein binding to the NP surface, which forms a protein coating that is called the “protein corona”. To simplify studies of protein–NP interactions and protein corona formation, NPs are incubated with biological solutions, such as human serum or human plasma, and the effects of this exposure are characterized in vitro. Yet, how NP exposure to these two different biological milieus affects protein corona composition and cell response has not been investigated. Here, we explore the differences between the protein coronas that form when NPs are incubated in human serum versus human plasma. NP characterization indicated that NPs that were exposed to human plasma had higher amounts of proteins bound to their surfaces, and were slightly larger in size than those exposed to human serum. In addition, significant differences in corona composition were also detected with gel electrophoresis and liquid chromatography–mass spectrometry/mass spectrometry, where a higher fraction of coagulation proteins and complement factors were found on the plasma-exposed NPs. Flow cytometry and confocal microscopy showed that the uptake of plasma-exposed NPs was higher than that of serum-exposed NPs by RAW 264.7 macrophage immune cells, but not by NIH 3T3 fibroblast cells. This difference is likely due to the elevated amounts of opsonins, such as fibrinogen, on the surfaces of the NPs exposed to plasma, but not serum, because these components trigger NP internalization by immune cells. As the human plasma better mimics the composition of the in vivo environment, namely blood, in vitro protein corona studies should employ human plasma, and not human serum, so the biological phenomena that is observed is more similar to that occurring in vivo.     

Personalized liposome–protein corona in the blood of breast,gastric and pancreatic cancer patients

When nanoparticles (NPs) are dispersed in a biofluid, they are covered by a protein corona the composition of which strongly depends on the protein source. Recent studies demonstrated that the type of disease has a crucial role in the protein composition of the NP corona with relevant implications on personalized medicine. Proteomic variations frequently occur in cancer with the consequence that the bio-identity of NPs in the blood of cancer patients may differ from that acquired after administration to healthy volunteers. In this study we investigated the correlation between alterations of plasma proteins in breast, gastric and pancreatic cancer and the biological identity of clinically approved AmBisome-like liposomes as determined by a combination of dynamic light scattering, zeta potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) and semi-quantitative densitometry. While size of liposome–protein complexes was not significantly different between cancer groups, the hard corona from pancreatic cancer patients was significantly less negatively charged. Of note, the hard corona from pancreatic cancer patients was more enriched than those of other cancer types this enrichment being most likely due to IgA and IgG with possible correlations with the autoantibodies productions in cancer. Given the strict relationship between tumor antigen-specific autoantibodies and early cancer detection, our results could be the basis for the development of novel nanoparticle-corona-based screening tests of cancer.     

Impacts of a Silver‐Coated Future

Silver is a compound that is well known for its adverse environmental effects. More recently, silver in the form of silver nanoparticles (Ag NPs) has begun to be produced in increasingly larger amounts for antibacterial purposes in, for instance, textiles, wound dressings, and cosmetics. Several authors have highlighted the potential environmental impact of these NPs. To contribute to a risk assessment of Ag NPs, we apply a suggested method named “particle flow analysis” to estimating current emissions from society to the environment. In addition, we set up explorative scenarios to account for potential technology diffusion of selected Ag NP applications. The results are uncertain and need to be refined, but they indicate that emissions from all applications included may increase significantly in the future. Ag NPs in textiles and electronic circuitry may increase more than in wound dressings due to the limited consumption of wound dressings. Due to the dissipative nature of Ag NPs in textiles, the results indicate that they may cause the highest emissions in the future, thus partly confirming the woes of both scientists and environmental organizations. Gaps in current knowledge are identified. In particular, the fate of Ag NPs during different waste‐handling processes is outlined as an area that requires more research.     

Influence of phytochemicals on the biocompatibility of inorganic nanoparticles: a state-of-the-art review

Inorganic nanoparticles (NPs) are among the most produced NPs that could be used in consumer products and as healthcare materials, however, the intrinsic toxicity particularly through the mechanism associated oxidative stress raises the health concern about inorganic NP exposure. Phytochemicals are bioactive metabolites derived from plants as well as non-pathogenic microorganisms living within plants and have been shown to be beneficial to human health with their anti-aging, anti-cancer, anti-inflammation and anti-oxidant properties. In the present review, the influence of on the biocompatibility of inorganic NPs was discussed. It has been shown that phytochemicals could be used as bio-friendly capping agents for green synthesis of inorganic NPs, and phytochemical coated inorganic NPs were remarkable stable and biocompatible with high therapeutic efficiency. Meanwhile, the presence of phytochemicals was also able to reduce the side effects and enhance the therapeutic abilities of inorganic NPs, which is likely attributed to the anti-oxidative properties of phytochemicals. Thus, using phytochemicals could be a promising and plausible way to reduce side effects and increase the biocompatibility of inorganic NPs for biomedical applications.     

Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise.

Emerging evidence indicates that exercise training can provide significant protection against myocardial ischemia-reperfusion injury. In this brief review, we provide a synthesis of current literature in the field and summarize the findings to date. Our intent is to identify the unique elements of cardioprotection acquired by exercise, and to illustrate what distinguishes this physiological acquisition of cardioprotection from all other known types of acquired cardioprotection. Finally, we point to future directions for research in this exciting area.     

Inorganic nanoparticle-based contrast agents for molecular imaging

Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future.     

Nanoparticulate drug delivery systems for cancer chemotherapy

Nanoparticles (NPs) are, in general, colloidal particles, less than 1000 nm, that can be used for better drug delivery and prepared either by encapsulating the drug within a vesicle and or by dispersing the drug molecules within a matrix. Nanoparticulate drug delivery systems have been extensively studied in recent years for spatial and temporal delivery, especially in tumour and brain targeting. NPs have great promise for better drug delivery as found in both pharmaceutical and clinical research. As a drug carrier, NPs have significant advantages like better bioavailability, systemic stability, high drug loading, long blood circulation time and selective distribution in the organs/tissues with longer half life. The selective targeting of NPs can be achieved by the enhanced permeability and retention effect (EPR-effect), attaching specific ligands, or by making selective distribution due to change of the physiological conditions of specific systems like nature, pH, temperature, etc. It has been observed that drug-loaded NPs can have selective distribution to organs/tissues using different types of and proportions of polymers. The current aim of researchers is to prepare NPs that are long-lived with and that demonstrate the appropriate selective distribution for better therapy and thus improved clinical outcomes. Nanoparticulate drug delivery systems have the potential to deliver a drug to the target site with specificity and to maintain the desired concentration at the site for the intended time without untoward effects. In this review article, the methods for the preparation of NPs, their characterization, biodistribution, and pharmacokinetic characteristics are discussed.     

Nanoparticulate drug delivery systems for cancer chemotherapy

Abstract

Nanoparticles (NPs) are, in general, colloidal particles, less than 1000 nm, that can be used for better drug delivery and prepared either by encapsulating the drug within a vesicle and or by dispersing the drug molecules within a matrix. Nanoparticulate drug delivery systems have been extensively studied in recent years for spatial and temporal delivery, especially in tumour and brain targeting. NPs have great promise for better drug delivery as found in both pharmaceutical and clinical research. As a drug carrier, NPs have significant advantages like better bioavailability, systemic stability, high drug loading, long blood circulation time and selective distribution in the organs/tissues with longer half life. The selective targeting of NPs can be achieved by the enhanced permeability and retention effect (EPR-effect), attaching specific ligands, or by making selective distribution due to change of the physiological conditions of specific systems like nature, pH, temperature, etc. It has been observed that drug-loaded NPs can have selective distribution to organs/tissues using different types of and proportions of polymers. The current aim of researchers is to prepare NPs that are long-lived with and that demonstrate the appropriate selective distribution for better therapy and thus improved clinical outcomes. Nanoparticulate drug delivery systems have the potential to deliver a drug to the target site with specificity and to maintain the desired concentration at the site for the intended time without untoward effects. In this review article, the methods for the preparation of NPs, their characterization, biodistribution, and pharmacokinetic characteristics are discussed.     

PCSK9结构与功能

前蛋白转化酶枯草溶菌素9（PCSK9）基因属于前蛋白转化酶（PC）家族,由信号肽、前结构域、催化结构域和羧基末端结构域组成.大量研究发现,PCSK9能介导低密度脂蛋白受体（LDLR）降解,调节血浆LDL胆固醇（LDL-C）水平;而PCSK9的两类主要突变,功能获得型、功能缺失型可分别导致高胆固醇血症和低胆固醇血症. 因而研究PCSK9对相关心血管疾病的防治有重要意义. PCSK9结构特性与其生化功能密切相关,突变致使其调节胆固醇代谢的机制更为复杂.本文旨在总结PCSK9结构与功能的分子生物学特性,并指出目前研究中存在的问题,以利对PCSK9的进一步探索.     

Vital roles of sustainable nano-fertilizers in improving plant quality and quantity-an updated review

Nanotechnology has received much attention because of its distinctive properties and many applications in various fields. Nanotechnology is a new approach to increase agricultural production with premium quality, environmental safety, biological support, and financial stability. Ecofriendly technology is becoming progressively important in modern agricultural applications as alternatives to traditional fertilizers and pesticides. Nanotechnology offers an alternative solution to overcome the disadvantages of conventional agriculture. Therefore, recent developments in using nanoparticles (NPs) in agriculture should be studied. This review presented a novel overview about the biosynthesis of NPs, using NPs as nano-fertilizers and nano-pesticides, the applications of NPs in agriculture, and their role in enhancing the function of biofactors. We also, show recent studies on NPs-plant interactions, the fate and safety of nanomaterials in plants, and NPs' function in alleviating the adverse effects of abiotic stress and heavy metal toxicity. Nano-fertilizers are essential to reduce the use of inorganic fertilizers and reduce their antagonistic effects on the environment. Nano-fertilizers are more reactive, can penetrate the epidermis allowing for gradual release, and targeted distribution, and thus reducing nutrients surplus, enhancing nutrient use efficiency. We also, concluded that NPs are crucial in alleviating abiotic stress and heavy metal toxicity. However, some studies reported the toxic effects of NPs on higher plants by induction of oxidative stress signals via depositing NPs on the cell surface and in organelles. The knowledge in our review article is critical in defining limitations and future perspectives of using nano-fertilizers as an alternative to conventional fertilizers.     

硫化铜纳米粒子应用于肿瘤诊断和治疗的研究进展

癌症是当今威胁人类健康的主要疾病之一。近年来提出的近红外光介导的光热治疗,能够对肿瘤组织进行定点清除并且对正常组织具有较低的毒副作用,为肿瘤的治疗提供了新的方法。开发具有良好生物相容性的高效光热偶联剂是发展光热治疗的首要条件。随着纳米技术的飞速发展,一些金属纳米结构由于具有独特的光学特性作为光热偶联剂被广泛应用到肿瘤的光热治疗中。然而,成本高昂、制备过程繁琐以及光热稳定性较差等不足,限制了这些纳米材料的进一步应用。最新报道的新型光热偶联剂半导体硫化铜纳米粒子(copper sulfide nanoparticles,CuS NPs),由于其具有制备工艺简单、成本低廉、突出的光热稳定性和良好的生物相容性等优势,成为了当今纳米医学领域研究的热点。本文主要综述了CuS纳米粒子在肿瘤光热治疗和影像诊断方面的应用研究,并对CuS纳米粒子在生物医学领域应用中存在的问题和未来的研究方向进行了展望。     

Conformational properties of intrinsically disordered proteins bound to the surface of silica nanoparticles

Background

Protein-nanoparticle (NP) interactions dictate properties of nanoconjugates relevant to bionanotechnology. Non-covalent adsorption generates a protein corona (PC) formed by an inner and an outer layer, the hard and soft corona (HC, SC). Intrinsically disordered proteins (IDPs) exist in solution as conformational ensembles, whose response to the presence of NPs is not known.

Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review

Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.