Light-Activated Mesoporous Silica Nanoparticles for Nanoimpeller-Controlled and Photodynamic Cancer Therapy
- Author(s): CHOI, EUNSHIL
- Advisor(s): Zink, Jeffrey I
- et al.
In the recent biomedical research, mesoporous silica nanoparticles (MSNs) prepared by sol-gel chemistry have useful applications in cancer treatment. This is because of several attractive aspects of the MSN such as uniform pores with tunable size, large surface area, ease in functionalization, and biocompatibility. Also when the pores are functionalized with organic molecules that are stimuli-responsive, a controlled release system can be obtained for storage and delivery of a wide range of drugs through the pores. Among many therapeutic MSNs, light-activated silica nanoparticles are advantageous because ease in applying light activation allows for control of the system at a distance and a desired time. MSNs discussed in this dissertation involve two different types of the photo-responsive behaviors of functional molecules: (1) controlled release of pore contents by azobenzene-based nanoimpellers, and (2) generation of reactive oxygen species (ROS) by porphyrin-based photosensitizers.
Nanoimpeller-controlled MSNs, which are a main focus of this dissertation, are discussed in Chapter 2-4. Nanoimpellers consist of photo-responsive azobenzene derivatives that are attached to the mesopores, and undergo photoiosmerization that results in dynamic wagging motions of the unbound termini and drives the expulsion of molecules from the pores. Controlled release of molecules is demonstrated in solution using fluorescent dyes (Chapter 2) and then in human cancer cells using an anticancer drug to induce cell death (Chapter 3). Various molecules having different water solubilities are tested in non-aqueous, aqueous, and intracellular environments as well (Chapter 4). The last part of the dissertation illustrates photosensitizer-functionalized MSNs for photodynamic therapy (PDT). A photosensitizer porphyrin derivative that is bonded to the pore wall is operated to generate singlet oxygen by light irradiation to treat malignant cells (Chapter 5).