Engineering neodymium-sensitized nanoconstructs for near-infrared enabled photomedicine

• Main Author: Yu, Zhongzheng
• Other Authors: Timothy Tan
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Engineering::Bioengineering
• Online Access: https://hdl.handle.net/10356/136621
• Institution: Nanyang Technological University

Lanthanide-doped nanoconstructs have gained increasing attention in recent decades due to their unique properties, especially optical properties. The design of various lanthanide-based nanosystems are expected to contribute to medical and health applications, due to their advantageous properties such as excellent photostability, non-photobleaching and low cytotoxicity, etc. Among all kinds of lanthanide ions, neodymium (Nd3+) ions are highly favorable since they can absorb near-infrared light, specifically at 808 nm, and upconvert them to higher-energy light or heat. This biological transparent absorption can overcome the heating up effect caused by conventional ytterbium (Yb3+) ions sensitization. However, the low conversion efficiency and potential long-term toxicity of Nd3+-sensitized nanoconstructs are huge obstacles to their clinical translations. This thesis has contributed to this field in the design and fabrication novel Nd3+-sensitized nanoconstructs for near-infrared (NIR) enabled photomedicine, making them potentially safer, more efficient and closer to clinical usage. First of all, sandwich-structure ultrasmall (<10 nm) Nd3+-sensitized upconversion nanoparticles (UCNPs) have been synthesized for the first time to exploit the benefits of ultrasmall nanoparticles while maintaining a relatively strong blue emission. We adopt a combinatorial strategy of energy migration manipulation and crystal lattice modification, creating ultrasmall-superbright Nd3+-sensitized nanoparticles with 2 orders of magnitude enhancement in upconversion luminescence. Furthermore, we apply the nanoparticles to 808 nm light-mediated drug release. The results indicate time-dependent cancer cells killing and better antitumor activities. These ultrasmall-superbright dots have unraveled more opportunities in upconversion photomedicine with the promise of potentially safer and more effective therapy. Furthermore, we have tuned the configuration of tetralayer Nd3+-sensitized UCNPs in a fixed size for the first time. Specifically, we tune the thickness of sensitizing layer containing Nd3+ ions and inert layer of gadolinium (Gd3+) ions in a fixed combined thickness of 5 nm in tetralayer UCNPs to exclude size effect and enhance 4-photon conversion (360 nm, UV emission) process. An optimal combination of thickness of sensitizing and inert layer is uncovered to be 3 and 2 nm respectively, showing a new strategy of balancing sensitization and surface passivation to enhance 4-photon emission, while 3-photon emission (475 nm, blue) is mainly influenced by the overall nanoparticle size and its emission intensity remains similar in all the tetralayer UCNPs. In addition, 808-nm cross-linked hydrogel has been demonstrated. Our results have uncovered the structural parameters for optimal UV upconversion emissions and provided design guidance for lanthanide nanostructural configuration. Taking advantage of the low photon conversion efficiency of UCNPs, the last part of this thesis demonstrates the boosting the nonradiative process by generating new cross-relaxation pathways. Cross-relaxation among sensitizers is commonly regarded as deleterious in fluorescent materials, although favorable in photothermal agents. Herein, we coat Prussian blue (PB) on NaNdF4 nanoparticles (NdNPs) to fabricate core-shell nanocomplexes with new cross-relaxation pathways between the ladder-like energy levels of Nd3+ ions and continuous energy band of PB. The photothermal conversion efficiency was improved significantly and the mechanism of the enhanced photothermal effect was investigated. In vivo photoacoustic imaging and photothermal therapy demonstrated the potential of the enhanced photothermal agents. Moreover, the concept of generating new cross-relaxation pathways between different materials is proposed to contribute to the design of all kinds of enhanced photothermal agents. In summary, this thesis has provided some novel strategies to fabricate Nd3+-sensitized nanoconstructs to enhance the upconversion efficiency or photothermal conversion efficiency. We hope the strategies and studies presented in thesis can further enhance the attractiveness of lanthanide-based materials towards clinical translation.