Project Summary/Abstract
This proposal describes a research and training program to advance my academic career in biofilm treatment
and facilitate my transition towards independence. Over the past years, I have acquired a broad scientific
background and extensive research experience in multiple fields, including synthesis of nanomaterials,
chemistry, substrate-based nanocrystals, nanomedicine, in vitro and in vivo imaging. My long-term career goal
is to develop nanomaterials with different shapes, sizes, and compositions for biofilm-associated diseases. This
proposal was therefore designed to strengthen and diversify my nanomaterial synthesis and characterization
skills, complementing them with training in infection diseases and therapies.
During my postdoctoral training period, I have developed a unique structure termed Wulff in cage
nanoparticles (WICN) that integrate the competencies of both cage and core structures to allow their use as
contrast agents for photoacoustic imaging, computed tomography and photothermal therapy (PTT). Using these
structures, I have shown that their PTT properties are critically affected by shape, size and the plasmonic
properties of nanoparticles. Therefore, systematically studying the therapeutics applications of these unique
morphologies, particularly towards infection diseases, is an imperative step towards improving nanotherapeutics.
To that end, here I propose to exploit new photothermal nanoparticles (PTNP) with nanoshell, nanocage or
nanoframe morphologies and different compositions (Ag, Au, Pt, and Pd) which enhance photothermal behavior
and result in effective and rapid dental caries, wound and skin infection treatments (Aim 1, K99). This
photothermal effect of nanoparticles enables both precise spatial control and whole tissue irradiation, while being
a rapid treatment. The developed morphologies will be used to examine the anti-biofilm efficacy and
biocompatibility of the PTNP in vitro. In this aim, PTNP will be assessed for their antibacterial properties to reduce
oral and wound infections while accelerating the photoablation rates (Aim 2, K99-R00), I will select the most
effective formulation to follow the in vivo research in (Aim 3, R00). The knowledge acquired in Aims 1 and 2 will
be applied to enhance the photothermal ablation of biofilms in vivo as a flexible, fast and low cost treatment
method. We will test PTNP in an animal model using rodent models of dental caries and excisional wound model
to investigate the effect of light and heat generation on biofilms in vivo. We will confirm that photothermal
treatment and the anti-biofilm effect of developed structures could be a substitute to the use of broad-spectrum
antibiotics to heal wound infection, prevent dental caries and kill the bacteria while irradiating with NIR light.
To guide me in this undertaking, I have assembled a multidisciplinary mentoring team. At University of
Pennsylvania, Dr. Cormode (Primary Mentor, a leading scientist in Nanomedicine) from the Radiology
department , Dr. Koo (Co-mentor, biofilm-associated oral diseases expert) from the Department of Orthodontics
and Dr. Grice (Co-mentor, biofilm-associated skin diseases expert) from the Department of Dermatology will
continue mentoring me on in vitro and in vivo experiments. They will support my research activities and also
guide my transition to independence. These departments will provide resources and support to conduct
laboratory research, and foster my career development to achieve my goals.
