| dc.description.abstract | Micron/nano sized machines promise precise targeting and drug-delivery at hard to reach places inside the human body. There have been tremendous efforts in this direction and various remotely powered artificial nanomachines have been designed and experimented during the last decade by researchers. In this thesis, we explore the possible applications of magnetically driven artificial nanomotors under in-vivo conditions. We have demonstrated through a series of experiments, a synergistic application potential of nanomotors where they can sense localized changes in viscosity in fluids, discover new physico-chemical phenomenon in complex tumor-like environments and deliver therapy in hard-to-reach bacteria-infected rigid dental tissues.
First, we will discuss the ability of nanomotors to measure viscosity for Newtonian as well as non-Newtonian fluids in heterogenous environments– a development that would be especially useful in biophysical measurements, such as a tissue. We demonstrate, by imaging the orientational dynamics of nanomotors under the action of a rotating magnetic field, measurement of the viscosity of a fluid. This, when combined with the remotely controlled maneuverability of a nanomotor, allows us to observe the real-time spatial viscosity changes while the nanomotor swims through a heterogenous mixture of fluids. It was also possible to measure the temporal variation of the viscosity, achieved through controlled temperature changes in the microfluidic device.
Next, we describe how maneuvering nanomotors allow us to study cancer induced heterogeneity in a tumor model. We have moved the nanomotors through the complicated landscape of extracellular matrix using specially designed thinner nanomotors matched to the porosity of the protein mesh found in such matrix scaffolds. Nanomotors are found to adhere to the matrix secreted by cancer cells, whereas they were observed to move past normal cells. Investigating the cause for this adhesion led us to the discovery of the presence of sialylated charged matrix secreted by cancer cells in the extracellular matrix. Quantification of the adhesive force shows a correlation with the metastatic potential of the cell lines used for our experiments. We also found cell line specific anisotropy in the distribution of sialylated proteins. The adhesion of nanomotors to cancer secreted matrix, open a new way to sense and target cancer cells with minimum effort. We discuss the possibility of using this natural variation in nanomotor motion to detect and localize our agents near cancer cells in a mass of tissue containing both cancerous and non-cancerous cells.
Having demonstrated the sensing capabilities of nanomotors, where a swarm of nanomotors swimming through a modelled mass of tumor could localize themselves near cancer cells while minimally affecting the normal cells, we now discuss the therapeutic capabilities of this powerful experimental system. We specifically focus on hyperthermia as a treatment modality and show how special magnetic coating may render them as effective agents of magnetic hyperthermia. We observe hyperthermia induced cell death in real time and study the dynamics of death in cells. This required the construction of a new experimental system that can image inside the hyperthermia setup. A microscope with non-metallic parts was built and used to observe cells under hyperthermia. We also successfully use localized heat to demonstrate motion in freshly dissected tissue. Magnetic hyperthermia using nanomotors cause localized denaturation of collagen matrix in tissues, allowing nanomotors to carve out a path through such complex terrains. The method discussed here could pave the way for motion of nanomotors in live animals in future.
Finally, we discuss how the maneuverability and therapeutics capabilities of nanomotors can be used to solve a problem of clinical relevance. Reinfection of the dentine tissue after a root canal procedure occurs for ~20% of cases and may cause further complications in older patients. The main cause for such endodontic reinfection is persistent bacteria (especially E. faecalis) in the tubules of the dentine tissues. E. facecalis is multi-drug resistant and current state-of-the-art treatment procedure is ineffective – relying on diffusion of corrosive sodium hypochlorite to reach the depths of such tubules. We show how nanomotors can be effectively used to reach hard-to-reach depths of the tunnels naturally formed in the dentinal tissue found in human teeth. We further show how magnetic hyperthermia can be used to treat these resistant bacteria, thus eliminating the need for corrosive chemicals or antibiotics. The application of nanomotors here solves the dual problem of targeting and therapeutics, not addressed by conventional treatment procedures, and has the promise of better treating endodontic reinfection. | en_US |
