A drug-free theranostic approach for localized and systemic diseases via nanoparticles

The emergence of field of nanomedicine for addressing the biomedical challenges created a toolkit which has been evolving dynamically with the advances in the medicine itself. At the heart of nanomedicine, nanoparticles exist which are envisioned to shift the paradigm of conventional therapy by furnishing the field with their unprecedented properties. On top of the promising features, nanoparticles can also simultaneously be endowed with imageability to track the success of therapy and hence a subfield in nanomedicine called “theranostic” advened in recent years. However, the obstacles in the translation of the nanoparticles such as batch to batch variation during scale-up, the lack of control over cargo release and particle instability slowed their application in real life. An approach is proposed here where these challenges can be overcome by designing nanoparticles which are inherently therapeutic without the encapsulation of the secondary drug while they can also be imaged by various imaging modalities. These nanoparticles are based on carbon dots and hafnium oxide which can be imaged with fluorescent imaging and CT imaging as two major imaging modalities in the clinic. The surface-modified nanoparticles were utilized in this thesis to work out the localized diseases (dental biofilm, bone microdamage) and systemic diseases problems. At first, I applied strategies from materials science to modify the chemical properties of the carbon dots and worked towards the improvement of their interaction with the cells/ cellular components. I next demonstrated that the chemical properties of these nanoparticles can be tuned easily depending on the desired outcome for multiscale, multicolor imaging. Then, I geared towards the specific biomedical issues which can benefit from these nanoparticles. I presented the work on using nanoparticles of hafnium for the detection of the dental plaque by typical dental X-ray device based on a molecularly targeted approach toward carious bacteria. The therapeutic antibiofilm properties of these nanoparticles were established as well by comprehensive in vitro and in vivo studies. The inherently therapeutic nanoparticles of carbon which target the pH of the biofilm were investigated in the follow-up study without changing the diversity of the oral microbiota. The nanoparticles developed in the previous chapters were aptly surface functionalized and were used to target the bone microdamage in the following chapter. The distinct X-ray characteristic of the hafnium oxide nanoparticles made the detection of the damage viable in vivo using advanced CT technologies. Moreover, we showed that the nanobeacons of carbon dot can be used in the fluorescent microscopic evaluation of the bone damages ex vivo. Finally, the nanoparticle of inherently therapeutic carbon dots derived from certain algae was suggested to be used as activatable agents for the UV therapy of the cancerous skin cells. Together, these studies present the promise of the ‘inherently theranostic’ nanoparticles for the health-related issues. Therefore, the conveyed message which is built throughout this thesis is the unlimited opportunities for these agents which can be extended to the realm of the medicine itself.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2019

Author dc:creator

• Ostadhossein, Fatemeh

Contributors dc:contributor

• Pan, Dipanjan
• Murphy, Catherine Jones
• Dobrucki, Wawrzyniec
• Nie, Shuming

• Nanoparticles, drug free approach, therapy, imaging, diagnosis

Statement dc:rights

• Copyright 2019 Fatemeh Ostadhossein

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/105143

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/105143