Theranostic Nanocomposites For Multimodal Imaging And Photothermal Tumor Ablation

In recent years, photothermal therapy(PTT) has attracted tremendous interest in tumor ablation, owing to their unique advantages such as non-invasiveness, localized treatment and high efficacy. PTT utilizes near-infrared(NIR) light-absorbing nanoagents to achieve local temperature elevation for destruction of cancer cells. Irradiation can be applied on localized tumor area, resulting decreased systemic toxicity during cancer treatment. Therefore, PTT is considered to be a potential alternative to surgery for cancer treatment.Nanomaterials for PTT cancer treatment have been receiving more attention from researchers globally in recent years. Various types of nanostructures have been explored as photothermal agent such as Au nanoparticles, carbon nanomaterials, conjugated polymers, NIR dyes containing nanocomplexes. However, it is still a big challenge to establish one nanoparticle combinating the functions of multimodal imaging and photothermal therapy.Herein, driven by an optimized protein-based biomineralization method, firstly, we construct smart Cypate-grafted gadolinium oxide nanocrystals(Cy-Gd NCs) with cancer targeting capacity for trimodal(NIR fluorescent) NIRF/(photoacoustic) PA/(magnetic resonance) MR imaging and p H-responsive PTT. Furthermore, we employ the same albumin-based biomineralization approach to synthesize copper-based protein nanoparticles. Combined with different elements including S, Se, and Te, the absorption of copper-based protein nanoparticles can be adjusted to NIR region for more efficient tumor ablation. These investigations are shown as follows:Chapter 1. This chapter is an overall introduction of photothermal therapy as well as studies on different kinds of photothermal agents.Chapter 2. We have successfully synthesized cyanine-grafted gadolinium oxide nanocrystals through an optimized biomineralization process for precise tumor localization via trimodal NIRF/PA/MR imaging, and simultaneously superior cancer therapy via p H-responsive PTT. Cy-Gd NCs with the hydrodynamic diameter of 20.3 nm display enhanced photostability, cell internalization and tumor accumulation, and exhibit multiple imaging features including ultrasensitivity, precise anatomical localization, and good spatial resolution, which synergistically achieve the multimodal imaging with precise tumor localization. Meanwhile, Cy-Gd NCs exhibit p H-responsive photothermal effect, enhanced tumor accumulation, and preferable cellular uptake, which together result in effective tumor ablation in vivo without re-growth.Chapter 3. We synthesized two kinds of copper-based protein nanoparticles for efficient tumor ablation, Cu S protein particles(Cu SNCs) and Cu Se protein nanoparticles(Cu Se NCs), through a similar optimized biomineralization process. Cu SNCs and Cu Se NCs with hydrodynamic diameters of 35.1 nm and 23.5 nm exhibit efficient photothermal effect in solution, as well as ultrastable photostability, enhanced cell internalization and tumor accumulation. Cu SNCs and Cu Se NCs could induce severe cell damage under NIR irradiation, and thus generate efficient PTT tumor ablation upon photoirradiation after a single-dose intravenous injection without re-growth.In summary, we fabricated the organic-inorganic hybrid nanocomposites through an optimized biomineralization process, and explored their applications in multimodal imaging and photothermal tumor ablation. The multifunctional nanocomposites would have promising potentials in the field of cancer theranostics.