Microbial Nano-Biofactories: a Nanometric Trojan Horse with Biomedical Applications

Abstract

Antimicrobial resistance to antibiotics (AMR) and drug-resistant tumors have become some of society's most important concerns nowadays. The burden of these two problems is continuously increasing due to the overuse and misuse of antibiotics and the misdiagnosis and mistreatment of several tumor types. Although effective, current treatments are not free of drawbacks, such as the lack of selectivity or cytotoxicity issues, which tremendously impact the health of the patient and those around them in the community. As such, novel alternatives have been explored over time tailored to these specific problems. Among all of them, nanotechnology appears as a suitable platform with the potential to unlock both targeted delivery and a sustained release of either the antimicrobial or anticancer agents. Still, nanoscale materials show some problems, especially related to body clearance when used as systemic agents or to toxicity effects. Consequently, alternatives within the field have appeared over the past few years, and among all of them, Green Nanotechnology offers a compelling candidate to solve most of the problems associated with the biomedical use at the nanoscale. Commonly understood as the use of living organisms and natural products as raw materials, Green Nanotechnology is presented as a quick, environmentally friendly and cost-effective platform for the generation of nanomaterials with a wide range of compositions and physicochemical properties without the associated problems of their chemically-produced counterparts. In this thesis, two Green Nanotechnology-based approaches have been conceptualized, developed, and explored to produce nanomaterials with biomedical applications using bacterial and human cells. This manuscript's content renders essential advances in the establishment of these two technologies as suitable and reproducible nanomaterial synthesis methods with both antibacterial and anticancer abilities, with a complete array of characterization techniques and toxicity assays. Besides, the selectiveness of these agents is explored, for the first time, and correlated to the composition of the protein corona surrounding the nanospheres as a product of the synthesis method. Therefore, the main objective of this thesis is to show that Green Nanotechnology-based approaches, and especially those methods involving microorganisms (both bacterial and human cells), are suitable platforms for the production, implementation, and delivery of nanomaterials in biological systems with the promise of delivering a suitable solution for both AMR and drug-resistant tumors in a laboratory and industrial setting.