Bacterial derived nanovesicles for drug delivery and vaccine applications

• Main Author: Chua, Shae-Linn
• Other Authors: Czarny Bertrand Marcel Stanislas
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Engineering::Materials::Biomaterials
• Online Access: https://hdl.handle.net/10356/166584
• Institution: Nanyang Technological University

Antimicrobial resistance is one of the most urgent global challenges we face today. Traditional efforts of discovering and synthesising new antibiotics is facing a bottleneck, and cannot keep up with the rate at which bacteria newly acquires resistance genes. It is hence imperative to rely on alternative solutions such as the use of better drug delivery systems to deliver antimicrobials, and vaccination against common pathogens, reducing the need to use antimicrobials in the first place. For this, bacteria extracellular vesicles offer a unique solution due to their advantageous properties of being immunogenic, involved in inter-bacterial communication, and posing the ability to carry a wide range of therapeutic cargo. However, the process of isolating natural bacteria extracellular vesicles is often time consuming and produces a low yield. Hence, this project aims to explore the potential of mimetic bacteria extracellular vesicles produced via a mechanical shearing method. In this project, we successfully optimised the method to produce mimetic vesicles from Streptococcus Pneumonia and Staphylococcus Aureus, resulting in high protein and particle yields as as compared to natural extracellular vesicles isolated from the same bacteria. While these vesicles displayed no innate antibacterial activity against Streptococcus Pneumonia, Staphylococcus Aureus and Klebsiella Pneumonia, significant uptake of both mimetic and natural vesicles were observed in gram-positive Streptococcus Pneumonia and Staphylococcus Aureus bacteria. This highlights their potential for use as antimicrobial drug delivery systems. Furthermore, MTT assay with RAW264.7 macrophage cells showed that mimetic vesicles displayed lower cytotoxicity as compared to natural vesicles, demonstrating the advantage of using mimetic vesicles. Results from RT-qPCR experiments also showed that mimetic and natural vesicles were able to induce similar levels of innate and adaptive immune response.