Nanoparticle-aided delivery for tracking and controlling cell fate decisions in complex environments:A study in Pharmaceutical Sciences

Tissue engineering and regenerative medicine (TERM) aim to repair damaged or lost tissues such as heart, neuronal, vascular, and muscle tissues or organs to restore normal biological functions. While tissue engineering mainly utilizes an integrative approach with biomaterials such as scaffolds or hydrogels combined with cell populations from different sources and bioactive molecules, regenerative medicine also involves attempts to recruit autologous bodily functions. Although a lot of major milestones have been achieved to date, there are still challenges related to low cell survival in vivo, revascularization of the implanted tissue/organs, or migration of cells into undesired locations after implantation. Novel nanotechnology-based strategies have been closely involved with TERM applications with the potential to improve success with versatile solutions: stem cell labeling for cell tracking of implanted cells, delivery of bioactive agents to target organs, and incorporating nanoparticles in scaffold fabrication for mechanical enhancement or/and supplying biochemical stimuli to guide effective tissue restoration.

Mesoporous silica nanoparticles (MSN) have been widely explored in nanomedicine, particularly for cancer treatment and other therapeutic settings for the delivery of various cargoes. Their widespread research interest in drug delivery is due to their distinctive structural properties, such as high surface area, tunable pore diameter and pore volume, narrow pore size distribution, and flexible surface modification opportunities. The porous structure of MSNs can store various hydrophilic and hydrophobic molecules of different sizes owing to their tunable pore sizes, and protect them from the environment to deliver the cargo directly into the target area. Surface properties of MSN are one of the main characteristics that influence the cargo-nanoparticle interactions as well as biological activities in terms of blood circulation time, overcoming barriers and tissue penetrance, and enhanced cellular interactions.

The work of this thesis reports on various utilizations of MSNs for TERM applications, with an emphasis on the different surface modifications of MSNs to improve cell labeling efficiency, cell and tissue compatibility, hydrophobic drug delivery in vivo, and in formulating MSN-based nanocomposite matrix for guiding tissue repair. The findings reported in this thesis demonstrate that MSNs can be tailored to serve versatile applications for stem cell tracking and drug delivery to control cell behavior in vitro and in vivo, with remarkable potential to improve treatment outcomes and significantly improve the quality of life for patients.