Unique light responsive nanoplatforms for hypoxia therapeutic applications

• Main Author: Szeto, Dominic Mun Wai
• Other Authors: Xing Bengang
• Format: Thesis-Master by Research
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Science::Chemistry
• Online Access: https://hdl.handle.net/10356/150830
• Institution: Nanyang Technological University

Cardiovascular diseases are the prime causes of morbidity and mortality worldwide which strongly impacts resources and the economy causing a major burden on medical and public health systems. Currently, the most commonly utilised therapeutic strategy to circumvent these diseases is via surgical procedures but display several disadvantages such as high risk, expensive, invasive procedure, wound infection possibility and several weeks of recuperation required. Despite the great success of this approach, the development of new and improved strategies for efficient supply of oxygen to the myocardium are of paramount clinical relevance and a critical issue to explore. One possible method to generate deep tissue oxygenation is by triggering a photosynthetic reaction which requires light irradiation, a typical source of illumination for photosynthesis. However, photosynthesis cannot occur under dark conditions and normal light for photosynthesis possess extremely poor skin and tissue penetration abilities which severely restricts its ability in producing oxygen in deep tissue. While NIR light (700-1000nm), another source of illumination, which displays far improved deep tissue penetration ability may be used for photosynthesis but can only be effectively captured for photosynthesis using versatile luminescent NIR-to-UV/Vis responsive optical nanotransducers which can emit low wavelength, high intensity light upon NIR light excitation (e.g. at 980nm) with the converted emission at 465nm overlapping with chlorophyll pigment and thus promoting light harvesting photosynthesis in the dark. In this thesis project, an innovative and novel biological therapeutic system was designed by using a simple and effective NIR light-triggered oxygenator based on photosynthetic microalgae and lanthanide doped core-shell upconversion luminescent nano-transducers for the controlled oxygen production towards the therapeutic intervention of deep-tissue hypoxia. By utilising NIR light-triggered photosynthesis, as a proof-of-concept, microalgae photosynthetic therapy displayed 40-fold improved oxygen efficiency, in vitro oxygen production and no cell toxicity. This unique non-invasive laser therapy against deep-tissue hypoxic diseases presents a conceptual and practical paradigm shift in the way cardiovascular diseases are treated and displays a promising future for phototherapy using microbiotic nanomedicine.