Design, synthesis, and testing of carbon dot-based multifunctional nanoprobe for cancer theranostic and tissue engineering

Abstract

This thesis presents a comprehensive study on the design and synthesis of multifunctional nanoprobes using carbon dots (CDs) for cancer theranostics and tissue engineering applications. The research encompasses fundamental synthesis, unique property revelation, hierarchical surface engineering, and nano compositing approaches to achieve multifunctionality. Initially, a hydrothermal method was employed to produce multi-color emissive CDs with intrinsic ternary doping, which were further conjugated with folic acid (FA) for targeted bioimaging and photosensitization of human melanoma cancer cells. The resulting CD-FAs showed superior biocompatibility, photostability, and folate receptor-positive cancer cell targeting compared to folate receptor-negative ones. Next, a novel two-photon active carbon dot (CDcf) was synthesized by combining curcumin and folic acid, which exhibited improved efficacy for photodynamic therapy in oral cancer cells. CDcf demonstrated effective interaction with cancer cells via a folate-receptor-mediated pathway, leading to significant localization within the nucleus. Upon two-photon excitation, CDcf generated ROS within the nucleus, resulting in enhanced PDT efficiency and direct cancer cell destruction. Finally, CDs were integrated into a 3D printed PLGA nanocomposite scaffold to create a multifunctional platform. CDs enhanced the hydrophilicity of the scaffold, promoting cellular nesting and improved seeding efficiency and cell proliferation. The resulting PLGA-CD scaffold exhibited increased osteogenesis and bone mineralization, and the intrinsic luminescence of the composite allowed for label-free monitoring of cell proliferation and bone mineralization. The use of CDs significantly improved composite processability, customized fabrication of 3D printed scaffolds, stem cell differentiation, and bone tissue osteoconductivity, offering multifunctional benefits for bone tissue engineering.