Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical properties, including surface charge, hydrophobicity, and structural stability. However, there is insufficient understanding about the role of physicochemical properties of proteins in biomolecular corona formation. We hypothesized that the physicochemical properties of proteins would influence their interaction with nanoparticles and have a deterministic effect on nanoparticle-cell interactions. To test our hypothesis, we used model proteins from different structural classes to understand the effect of secondary structure elements of proteins on the nanoparticle-protein interface. Further, we modified the surface of proteins to study the role of protein surface characteristics in governing the nanoparticle-protein interface. For this study, we used mesoporous silica nanoparticles as a model nanoparticle system. We observed that the surface charge of proteins governs the nature of the primary interaction and the extent of subsequent secondary interactions causing structural rearrangements of the protein. We also observed that the secondary structural contents of proteins significantly affected both the extent of secondary interactions at the nanoparticle-protein interface and the dispersion state of the nanoparticle-protein complex. Further, we studied the interactions of different protein-coated nanoparticles with different cells (fibroblast, carcinoma, and macrophage). We observed that different cells internalized the nanoparticle-protein complex as a function of secondary structural components of the protein. The type of model protein had a significant effect on their internalization by macrophages. Overall, we observed that the physicochemical characteristics of proteins had a significant role in modulating the nanoparticle-bio-interface at the level of both biomolecular corona formation and nanoparticle internalization by cells.
The aim of this chapter was to understand the influence of nanoparticle challenge on physicochemical characteristics of the cells and to correlate these changes with cytotoxic response of nanoparticles. A nanoparticle surface charge and a concentration-dependent cytotoxic response were observed in the breast cancer cell lines MDA MB 231 and SKBR3. The cationic gold nanoparticles were more cytotoxic to cells as compared to anionic gold nanoparticles. It was also observed that cationic nanoparticles compromised the integrity of the plasma membrane at higher concentrations. Cationic nanoparticle challenge also caused changes in physicochemical characteristics of plasma membrane.Higher concentration of cationic nanoparticles caused an irreversible change in the surface charge density of cells. However, anionic gold nanoparticles did not show any such effect. It was observed that the ROS-mediated oxidative stress was the mechanism of cationic gold nanoparticle-mediated cytotoxic effect. Mitochondrial depolarization was observed in both anionic and cationic nanoparticle challenge. Therefore, the role of mitochondrial ROS in nanoparticle-mediated cytotoxicity is questionable. Finally, a generalized model involving modulation of intracellular Ca 2+ can potentially provide an explanation for the observed pluralistic response of the cells towards nanoparticle challenge.
Rabies is a global problem and is endemic in India. Rabies cases occur throughout the year, and the majority of cases are associated with dog bites. We report a rabies outbreak investigation in an urban area of Delhi conducted by our multidisciplinary team, and its role in proactively controlling a rabies outbreak by concerted efforts and timely advice to various stakeholders using a “One Health Approach.” A veterinary care NGO from Delhi picked up a suspected rabid stray dog and submitted a brain sample for diagnosis of rabies, as they had received information from a resident of the locality about an unprovoked animal bite incident involving a girl (category III bite) and close contact of two more stray dogs living in the vicinity of the suspected rabid dog. The laboratory diagnosis of rabies in the suspected dog brain sample was confirmed by using Fluorescence Antibody Test (FAT). A multi-expert investigation team with expertise in medicine, microbiology, veterinary sciences, laboratory diagnosis, and public health was constituted to investigate the outbreak. The timely, adequate, and appropriate anti-rabies management initiated for the animal bite victims in this incident could prevent rabies. Proactive involvement of multiple stakeholders and knowledge attributes and practice of local residents could prevent human rabies. As there were no further reports of dog bites from the area, the chain of rabies transmission in that area could be controlled. The presented work is a classical case scenario where concerted efforts of all stakeholders achieved effective control and prevention of rabies by adopting the “One Health approach”.
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