Towards fine-tuning the surface corona of inorganic and organic nanomaterials to control their properties at nano-bio interface

Designing nanomaterials for biological applications has become an emerging interdisciplinary area of science; however that raises the need to understand the materials interaction with different biological components at the nano-bio interface. Such basic understanding is required for the development of nanomaterials-based diagnosis, therapy and medicine. In this perspective, this thesis investigated development of new synthetic methodologies to control the surface corona and composition of nanoparticles in a single step. Specifically, tryptophan and tyrosine amino acids were employed to synthesize gold, silver and their bimetallic nanoparticles. These materials can be viewed as amino acid functional groups anchored onto nanoparticles corona, which can render these surfaces like artificial enzymes. Captivatingly, these nanomaterials exhibited peroxidise-like behaviour and this property was found to be composition, temperature and surface functionalization dependent. Furthermore, antibacterial studies demonstrated that toxicity against Gram positive bacteria ( Staphylococcus albus ) originated from the amino acid corona whereas the composition of nanoparticles didn’t play a significant role. Conversely, antibacterial activity against Gram negative bacterium ( Escherichia coli ) was found to be composition dependent and capping of amino acids had little influence. These findings established a strong correlation between the surface corona and metal composition of nanoparticles and their antibacterial activities against two different bacterial strains. Moreover, in order to demarcate how this surface functionalization plays a critical role in biological action; non-toxic Au nanoparticles were further chosen to reveal the significant influence of surface functionalization. Tyrosine reduced Au nanoparticles turn out to be a potential antibacterial agent after they were sequentially functionalized using polyoxometalates and lysine. Functional polyoxometalates imparted antibacterial potential on the surface of nanoparticles and the cationic nature of lysine worked as guide to target negatively charged bacterial cells. These nanoparticle-based functional antibacterial agents are seen to employ a physical mode of action against bacteria by causing pore formation, cell wall cleavage and cell lysis. The above-discussed inorganic nanoparticles are not suitable for DNA delivery applications due to their inherent toxicity as well as the long residence time of the inorganic nanomaterials within the living system. Therefore, DNA delivery vector requires an organic nanomaterial that could encapsulate the DNA. Another reason to choose organic nanostructures is they can be broken down by enzymatic reactions within the bacterial cells. In this context, organic materials based nanostructures were employed for DNA delivery applications and to understand their interaction with DNA. Tri-block copolymer (PEO 20- PPO 69- PEO 20 ) was used as the organic material and when pDNA was mixed along with the polymer, they formed self-assembled nanostructures that could be used as non-viral DNA delivery vehicles. The electrostatic interaction between the phosphate group (PO 4 3- ) of pDNA and the hydrophilic segments (PEO) of the polymer chains drive the self-assembly process. At 1:10 weight ratio of pDNA and polymer the bacterial transformation was found to be the maximum, leading to over six folds higher transformation efficiency. Furthermore, during transformation studies, the integrity and functionality of the green fluorescent protein (GFP) pDNA in nanostructures were also demonstrated within the cellular environment by the expression of GFP gene

Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations

Spectrally–selective monitoring of ultraviolet radiations (UVR) is of paramount importance across diverse fields, including effective monitoring of excessive solar exposure. Current UV sensors cannot differentiate between UVA, B, and C, each of which has a remarkably different impact on human health. Here we show spectrally selective colorimetric monitoring of UVR by developing a photoelectrochromic ink that consists of a multi-redox polyoxometalate and an e− donor. We combine this ink with simple components such as filter paper and transparency sheets to fabricate low-cost sensors that provide naked-eye monitoring of UVR, even at low doses typically encountered during solar exposure. Importantly, the diverse UV tolerance of different skin colors demands personalized sensors. In this spirit, we demonstrate the customized design of robust real-time solar UV dosimeters to meet the specific need of different skin phototypes. These spectrally–selective UV sensors offer remarkable potential in managing the impact of UVR in our day-to-day life

Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver

Audit Committee Characteristics and Financial Performance of Quoted Insurance Companies in Nigeria

The study investigated audit committee characteristics and financial performance in Nigerian insurance companies. The study adopted ex-post-facto research design. Utilizing data from eleven insurance companies listed on the Nigerian Exchange Group as at 31st December, 2023, the study employed purposive sampling to ensure comprehensive analysis. Descriptive statistics and Ordinary Least Squares regression analysis, facilitated by E-view-9 statistical package, are utilized for rigorous examination. Results revealed a significant positive association between audit committee size, composition, and Profit After Tax (PAT). However, the frequency of audit committee meetings revealed positive insignificant relationship with PAT. The findings underscored the importance of diverse and expert audit committee members, structured meeting schedules, and continuous training programs to enhance governance effectiveness and drive financial performance in the Nigerian insurance sector

Sequential surface functionalization by polyoxometalates and lysine renders non-toxic gold nanoparticles strong antibacterial agents

We demonstrate sequential surface functionalization of tyrosine synthesised gold nanoparticles (AuNPs) with polyoxometalates (POMs) and lysine. Antibacterial activities of these AuNPs and their nanoconjugates were evaluated toward Gram negative bacteria Escherichia coli. AuNPs were found to be non-toxic to the E. coli but after their surface functionalization with POMs, these AuNPs showed antibacterial activity due to the oxidative stress to the bacterial cells induced by POMs present on the surface of AuNPs. Lysine modified AuNPs-POMs nanoconjugates exhibited significantly higher antibacterial activity as cationic amino acid lysine directs these nanoconjugates toward negatively charged bacterial cells and provoke rupture of cell wall/membrane. Short incubation time was enough to observe the bactericidal action. By varying the surface functionlization of non-toxic AuNPs with POMs and lysine, we have shown the different levels of antibacterial action and their mode of action

Fine-tuning the antimicrobial profile of biocompatible gold nanoparticles by their sequential surface functionalization using polyoxometalates and lysine

Antimicrobial action of nanomaterials is typically assigned to the nanomaterial composition, size and/or shape, whereas influence of complex corona stabilizing the nanoparticle surface is often neglected. We demonstrate sequential surface functionalization of tyrosine-reduced gold nanoparticles (AuNPsTyr) with polyoxometalates (POMs) and lysine to explore controlled chemical functionality-driven antimicrobial activity. Our investigations reveal that highly biocompatible gold nanoparticles can be tuned to be a strong antibacterial agent by fine-tuning their surface properties in a controllable manner. The observation from the antimicrobial studies on a gram negative bacterium Escherichia coli were further validated by investigating the anticancer properties of these step-wise surface-controlled materials against A549 human lung carcinoma cells, which showed a similar toxicity pattern. These studies highlight that the nanomaterial toxicity and biological applicability are strongly governed by their surface corona

Amino acid and gold nanoparticles modified mesoporous silica materials synthesis and their applications in DNA transformation

Cytotoxicity and immunogenicity of viral DNA delivery vectors in DNA transformation raises the demand of developing non viral DNA delivery systems which can avoid these problems without compromising transformation efficiency. In this context, we have developed mesoporous silica nanoparticles as non-toxic DNA delivery vehicles. Mesoporous silica nanoparticles were synthesized by hydrolysing the tetraethylorthosilicate dissolved in an organic solvent by the amino acid lysine dissolved in aqueous medium and solid material obtained as a result of hydrolysis was calcined. In a similar manner, we have synthesized pure mesoporous silica nanoparticles (MSN) and gold nanoparticles incorporated silica nanomaterials. These materials designed to have very high surface area, tuneable pores and surface functionalisation in such a way to anchor high amount of DNA. Further, we demonstrate their transformation potential using E. coli DH 5α as a model microorganism used for genetic transformation by a bacterial plasmid that contains the gene for green fluorescence protein (GFP) and ampicillin resistance. Physically mixed pDNA and MSNs / functionalized MSNs were incubated for 2 hours at 37°C for complex formation in different ratios to identify the adequate concentration ratio that give high transformation. Gold functionalized MSNs (Au@MSN) were found to be the most efficient transformation vector due to affinity of gold nanoparticles to the DNA and their bigger pore size. By the use of MSNs and functionalized MSNs we have achieved low cytotoxicity and higher DNA transformation

Stabilization of polyoxometalates on gold nanoparticles surface using amino acid linker to control their toxicity

Polyoxometalates (POMs) have been used for antibacterial, antiviral and anticancer applications in in-vitro toxicological studies. These POMs induce oxidative stress at the cell surface and in the cytoplasm. However their instability at physiological pH, non specific binding, and high toxicity limits their direct application in biology and medicine. To circumvent that, we have developed a strategy to anchor them on a biocompatible carrier such as gold nanoparticles (AuNPs) by using an amino acid linker to regulate their stability and toxicity. AuNPs were synthesized by the reduction of gold ions using aspartic acid as reducing agent. These AuNPs were surface functionalized with cationic amino acid lysine to strongly anchor POMs. Subsequently, these lysine functionalized gold nanoparticles (AuNPsLys) were further modified with two POMs such as phosphotungstic acid (PTA) or phosphomolybdic acid (PMA). UV-visible, RAMAN, XPS, DLS and TEM studies were carried out to characterize these nanomaterials. Currently, we are exploring antibacterial, anticancer and other biological applications of these functionalized nanomaterials