Karl I. Jacob (Georgia Institute of Technology, School of Materials Science and Engineering)
Luke Brewster, MD, PhD (Emory University School of Medicine)
J. Brandon Dixon, PhD (Georgia Institute of Technology, George Woodruff School of Mechanical Engineering)
Mostafa A. El-Sayed, PhD (Georgia Institute of Technology, School of Chemistry & Biochemistry)
Krishnendu Roy, PhD (Georgia Institute of Technology, Wallace H. Coulter Department of Biomedical Engineering)
Microfluidic generation of cancer nanomedicines
Cancer diagnosis and therapy are perhaps the most promising areas for nanotechnology in medicine, and are expected to soon have applications in the market. The goal of this dissertation was to develop a technological foundation for synthesis and evaluation of polymer-based cancer therapeutic. This was performed using a microfluidic platform for optimization, and characterization of resulted particles for controlled drug release within the tumor environment. This technique was first optimized to show the feasibility of making drug-nanoparticles (NPs) out of different synthetic and natural polymers with it. The biophysical properties of these particles were also investigated at nano-biointerface. The process was then adjusted to develop pH-responsive core-shell NPs enabling oral administration of hydrophobic cancer therapeutics. This technique was also adjusted to fabricate complex NPs via controlled self-assembly of several components in a single step. Resulted particles can be used for theranostics applications or provide ultra-high drug loading capacity. Tuning the surface properties was also possible via this system and it was used to control immune-NPs and cancer cell-NPs interactions. To prolong blood circulation and enhance cell internalization, feasibility of making one-dimensional nanocarriers by template-based self-assembly approach was also confirmed. These nanocarriers can serve as suitable candidates for combinatorial cancer therapy as they can load and deliver substantial amounts of drugs while allowing for hyperthermia effect thanks to their carbon nanotube core. Mechanical properties of nanocarriers can also influence a broad range of NPs’ biological behaviors. Here, inspired by viruses, systematic investigation of the mechanobiological properties of NPs are done to determine the optimized range for in vitro and in vivo targeting. NPs with switchable mechanical properties are proposed capable of switching from soft to stiff state in the site of action and provide enhanced therapeutic efficiencies. Overall, we hope that this research provides broad information on how NP design can affect and control the efficacy of cancer nanomedicine. These findings point to the high potential of microfluidic platforms as engineering toolboxes that enable design of complex multifunctional nanomaterials via controlled bottom-up approach for various biomedical applications.