Exploring the roles of nanoparticles and microneedles in the bacteria management for topical applications

• Main Author: Cui, Mingyue
• Other Authors: Xu Chenjie
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Engineering::Bioengineering; Engineering::Environmental engineering::Water treatment
• Online Access: https://hdl.handle.net/10356/139170
• Institution: Nanyang Technological University

Bacteria are important prokaryotic microorganisms playing important roles in the balance of ecological equilibrium. The relationship between human beings and them is complicated. Pathogens can induce serious infections like pneumonia and sepsis, while the supplement of certain species helps to restore the healthy state of tissue or organ. However, few studies have been done from bacteria labeling, detection, to treatment systemically by collaboration with nanoparticles and microneedles, neither using bacteria to treat bacteria through the MN system. Over the past decades, various studies have been done based on the development of nano and microtechnology. Inorganic nanoparticles such as iron oxide NPs, silica NPs, zinc oxide NPs and titanium oxide NPs have been widely used owing to their lower cost, easier large-scale production and surface modification, as well as antimicrobial properties of zinc oxide NPs and titanium oxide NPs. MN has been an essential technology for the treatment of diseases by delivering cargoes percutaneously. In the first half of this thesis, the synthesis of various inorganic NPs is established for labeling, detection, and treatment separately. There is no doubt that NPs are essential in these applications owing to their extremely small size and big surface area. Here, silica NPs made of modified Pluronic polymers F108 were established and showed good performance in the labeling of both gram-positive and gram-negative bacteria. This system is versatile to be conjugated with various molecules, such as dye and recognition elements. Thereafter, bacteria were proposed to be quantified through competitive binding between negative charge enzyme and bacterial membrane. Enzymes were detached from the surface of NPs and were free to react with the colorimetric substrate CPRG to show purple to red color. The concentration of bacteria was directly proportional to the absorbance at 574 nm. The whole process could be finished in 2 hours if the samples are within the range of 103 to 108 CFU/mL. With the application of iron oxide NPs, bacteria were separated from the system simultaneously. Thus this system could be used for bacterial separation and bacterial quantification inside unknown samples. In the end, the antimicrobial property of zinc oxide NPs was tested by comparison of the treatment with SiO2, TiO2 and ZnO NPs. It was found that the ZnO group showed faster wound closure compared to other groups. The co-culture of ZnO NPs and bacteria also showed a significant decrease of OD600 proportional with the concentration of ZnO. When the number was to 1.0 mM, the OD600 was even lower than 0.1, 6 times lower than the group of TiO2. In the second half of this thesis, the fabrication of MNs with Zinc Oxide nanobushes is introduced first. With the generation of nanobushes on the surface of gold coated polystyrene MNs, antimicrobial properties of zinc oxide endow the system to decrease modal strains S. aureus and Salmonella by 6 or 5 times separately. Subsequently MNs were used further to deliver predatory bacteria and stored in low temperature to keep the viability of these bacteria. Predatory bacteria are essential in killing of gram-negative bacteria and proved to be safe and cleared by the system after work. In summary, nanotechnology and micro techniques are introduced in this thesis in the field of bacterial labeling, quantification and treatment systemically. Specifically, inorganic NPs like silica NPs, iron oxide NPs, zinc oxide NPs based systems are introduced here. The application of MNs is established subsequently, which provides a promising translational method to be used clinically in the future.