Biomimetic nanoparticles (NPs) are bio-inspired inorganic nanoscale materials that replicate some biological nanostructures functionalities including self-assembly, catalysis, and enzyme inhibition. These functionalities are being investigated for and, in some cases, are being utilized in optics and electronics such as chemical sensors, superhydrophobic coatings, and antireflective surfaces. This thesis examines the utilization of biomimetic inorganic NPs for various problems in biomedical engineering.

Specifically, in the first part of this thesis, I address the problem on controversial explanations of the antibacterial and other biological activity of zinc oxide NPs that are frequently utilized in cosmetics, textiles, and biomedical fields. In the second part of the thesis, I explore the self-organization of NPs into biomimetic supraparticles (SPs) for nucleic acid delivery that can be exploited as drug delivery agents.

NPs have been used in the antimicrobial field for a long time; however, their antibacterial mechanism of action against different types of bacteria remains unclear and, in many cases, misinterpreted. Most of the studies on antimicrobial NPs suggest reactive oxygen species (ROS) formation, ion release, and membrane damage as the primary source of antibacterial activity. In Chapter 2, we show that the mechanism of antibacterial activity for Staphylococcus aureus is remarkably more complex than generating ROS or the release of Zn2+ ions and is based on formation of biomimetic complexes of NPs with proteins. Gene expression analysis demonstrated that ZnO-NPs significantly affect carbohydrate metabolism and cell energetics, where the uridine monophosphate (UMP) biosynthesis pathway is highly upregulated. In Chapter 3, we explore the ZnO-NP mode of entry into S. aureus and the cell metabolism. Here, we showed that NPs enter the cells within 5 minutes of exposure and induce minimal membrane damage. We note that cells do not depolarize until 60 min post-NPs exposure. Thereby, we highlight that membrane damage is not the primary mechanism of action but rather a downstream effect of ZnO-NPs exposure to bacterial cells. Taken together, causing minimal ROS production and significant changes in carbohydrate metabolism and bioenergetics along with cell entry without immediate membrane damage imply the biomimetic function of these NPs. Further investigation into the antimicrobial mechanisms of biomimetic NPs is essential for future clinical translation.

Over the past few decades, there has been considerable interest in developing nanoscale constructs as effective delivery tools for high molecular weight drugs. In chapter 4, I explore the self-assembly of NPs into compartmentalized SPs, which mimics the structure of a virus to deliver nucleic acid into cells. The time-dependent self-assembly mechanism reveals that these SPs are formed from nanocup intermediates. We found that this intermediate stage is essential for the utilization of SP compartments. Nucleic acid is added to the system at this stage before SP formation, and high encapsulation is achieved. Similar to virus infections, once cells uptake the SP, SP disassociates in endosomes and releases the cargo.

Overall, the work presented in this thesis investigates and highlights the strong potential of biomimetic inorganic NPs use in next-generation biomedical applications.

Date: Monday, August 2, 2021
TIme: 1:00PM
Zoom: https://umich.zoom.us/j/95043183845
Chair: Prof. Nicholas Kotov