Bacteria- and citric-mediated synthesis of nanomaterials for biomedical applications

Abstract

The development of society and the progress of science and technology has brought to humankind an awareness of the importance of health. The rise of medicine and the birth of the healthcare system has given us a weapon to fight diseases that society has had for a long time- a seemingly never-ending fight. Nowadays, in particular, antibiotic-resistant bacterial infections and cancer are two of the main concerns that confronts the healthcare system. While the first one is derived from a well-known misuse and overuse of antibiotics, cancer has been always there, but cancer cells have been finding more efficient ways to spread and trick new treatments leading to chemotherapeutic-resistant cancer cells. Consequently, it is imperative that both problems are met with appropriate solutions, ones that may differ greatly from the current use of antibiotics and standard cancer treatments. The answer might lay beyond the macroscopic world. Nanotechnology and its combination with medicine are giving rise to a wide variety of biomedical options that may be more effective than any treatment humans have researched before. Because of their excellent increased surface area to volume ratios and high reactivity, those materials confined within the nanometric world are able to exert a stronger interaction with bacteria and cancer cells, which may affect their growth and propagation with a better outcome than that of current drug-based treatments. Nevertheless, beyond the application, remarkable progress has been found in the synthesis of these nanomaterials. For a long time, traditional synthetic chemical methods for nanomaterial synthesis, taking knowledge from both physics and chemistry, have been unable to meet the needs of both society and the environment. This has led to researchers to find green, low-cost and environmentally friendly methods for the efficient synthesis of different nanostructures. As a suitable answer, nature can offer a wide range of raw materials for the generation of nanomaterials, from living organisms, such as bacteria or plants, to biomolecules coming from large organic sources. Consequently, as a synergy between the chemistry of the elements and the properties of the natural sources, these green-synthesized nanomaterials are then able to possess novelty while being less toxic and posing less pollutants to both society and the 5 environment. From all the green nanotechnological methods possible, we decided to study what can be considered by far two of the most efficient green approaches for the generation of nanomaterials: bacterial cells and plants. The first part of this dissertation is focused on a Nanometric Trojan Horse (NTH) approach applied to the bacteria domain, focused on the synthesis of bacterial selenium (Se) nanoparticles by pathogenic Gram-negative and -positive bacteria, and the subsequent use of Se nanospheres as selective antibacterial agents towards the same bacterial strain that synthesizes them, with low cytotoxicity towards healthy human cells and potential as anticancer, antioxidant and biosensing agents. The nanosized selenium synthesized by bacteria themselves showed significant and continuous inhibitions to bacteria and cancer cells growth by up to 90%. On the other hand, the second half of this dissertation is focused on the plant component-based synthesis of tellurium (Te) nanomaterials using citric juices (orange, lemon, and lime) as unique reducing and stabilizing agents, with two main objectives: to set the basis and novelty for the largely-unknown biomedical applications of this forgotten metalloid, and to offer a cost-effective and environmentally-friendly approach for the generation of antibacterial, anticancer and antioxidant Te nanostructures with a bright future to enhance biomedical devices. The green-synthesized nanostructures showed significant antibacterial activity against both Gram-negative -Escherichia coli- and Gram-positive - Staphylococcus aureus- bacteria, in a range of concentrations from 5 to 50 μg/mL for 24 hours experiments. Nanoparticles were also tested for their cytocompatibility with human dermal fibroblast (HDF) cells for 24 and 48 hours, showing no significant cytotoxic effect at concentrations up to 50 μg/mL. Moreover, nanostructures were cultured with melanoma cancer cells for 24 and 48 hours, exhibiting a cytotoxic effect and inhibiting the average growth of cells within the same range of concentrations. Therefore, the work performed in this dissertation is aimed to enlighten the application of Green Nanotechnology for the synthesis of novel nanosized chalcogen nanomaterials as biomedical agents to help and serve the challenges that the healthcare system should face today.