Near infrared contrast agents for theranostic applications

In recent years, there has been a shift towards personalized medicine which is evidenced by the Food and Drug Administration (FDA) approvals[1]. One of the key principles of personalized medicine is the use of diagnostic tools such as imaging techniques to provide accurate information about the medical condition in order to prescribe the right treatment for the right person at the right time and dose. However, there are limitations to the current imaging techniques to achieve this aim, such as poor image resolution, high cost, and potential side effects. Optical imaging (OI) that uses near-infrared (NIR) light promises a minimally-invasive method of gaining accurate information by virtue of its deep penetration depth without background and biosafety issues. The aim of this thesis is to explore some of the NIR light responsive theranostics that are used in current diagnosis and therapeutics, such as NIR phototherapy and NIR-II fluorescence imaging. In particular, making use of the up- and down-photon converting features of lanthanide-doped nanoparticles (LNPs) not only achieves sensitive NIR optical sensing but also enables efficient therapeutic effects against deep-tissue disorders. Our first project introduces a NIR theranostic platform that was fabricated by Upconversion Nanoparticles (UCNPs) and the cyanobacteria, in which core-shell UCNPs, NaYF4:Yb/Tm (30:0.5)@NaYF4, are prepared via a hydrothermal method. It is subsequently modified with an amino-silica shell, followed by conjugating it to cyanobacteria, S. Elongatus. It is known that blue light is able to activate the photosynthesis pathway that is capable of oxygen gas (O2) generation thereby facilitating the management of ischemia or hypoxic damages. Such a promising NIR light-powered photosynthesis platform will allow the effective therapeutics in deep tissues and boost the phototheranostics into a brand new field. The second project presents a novel nanodiagnostics for ratiometric redox luminescence imaging in the second NIR window (NIR-II), which was fabricated by the energy transfer integration of Cerium ion (Ce3+)-sensitized LNPs, NaCeF4:Nd/Yb/Er(1:20:1). This type of LNPs uses the excitation of NIR light at 808nm while the emissions are at 1064 and 1530 nm. Upon the addition of an oxidant (e.g. hydrogen peroxide, H2O2), the emission intensity at 1530 nm would be reduced due to the oxidation of Ce3+ to Ce4+ which hinders Er3+ emission in the photon energy transfer process. Meanwhile, it may not affect the 1064 nm emission associated with Nd3+. Thus, the redox status could be determined by the ratio of Em1064/Em1530. However, the preliminary data showed that both of 1064nm and 1530nm emissions are quenched by H2O2. Future work to understand the mechanism of the redox-induced energy transfer inside LNPs will be necessary to allow for the development of more sensitive ratiometric NIR-II imaging probes of H2O2 as well as the understanding of the oxidative stress implications in living conditions. In summary, the development of the NIR contrast agents is able to provide broad perspectives for both bioimaging and therapeutic applications in sensitive and deep tissue resolutions. We believe that the works presented in this thesis may serve as an archetypal system to encourage innovative theranostics not only for pathological assessments but also benefit for the precise intervention of disorders.Master of Scienc