Author ORCID Identifier
0000-0003-1936-611X
Document Type
Dissertation
Date of Award
12-31-2022
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical and Materials Engineering
First Advisor
Kathleen McEnnis
Second Advisor
Prateek Shekhar
Third Advisor
Rajesh N. Dave
Fourth Advisor
Murat Guvendiren
Fifth Advisor
Xiaoyang Xu
Sixth Advisor
Treena Livingston Arinzeh
Abstract
Nanotechnology is a multidisciplinary field that has many different applications including cancer treatment and detection. Noble metal nanoparticles such as gold, silver or palladium, have shown major potential in the field of medicine and pharmaceutics. In particular, platinum nanoparticles (Pt NPs) have been reported with promising anticancer results. The activity of nanoparticles is based on their small size and high surface area; these properties allow them to penetrate biofilms as well as influence intracellular mechanisms. Recent studies indicate that Pt NPs can be used as a therapy for cancer showing a limited toxicity to healthy cells. Hence, in this work, a new treatment option for triple negative breast cancer (TNBC) based on Pt NPs is developed. TNBC is a type of breast cancer that lacks the three common receptors used for immunotherapy and with a tendency to metastasize faster. Consequently, TNBC has a worst prognosis and often chemotherapy is the only treatment option. However, chemotherapy is toxic, has many side effects and some cancers can even develop resistance, hence, new treatment options are needed to combat TNBC.
Drug delivery systems are technologies that help enhance circulation time or targeting at the tumor site. Therefore, to avoid accumulation in the liver or spleen a drug delivery system is proposed. Poly(lactide-co-glycolide) (PLGA) particles are synthesized as a delivery system for Pt NPs. The encapsulation of Pt NPs within PLGA nanoparticles is performed by nanoemulsion. Moreover, to enhance the circulation lifetime of the particles, surface modifications with polymers such as polyethylene glycol (PEG) can be performed. Surface modifications with PEG are a commonly used procedure to enhance circulation-time. Furthermore, active targeting by ligands of specific biomarkers, monoclonal antibodies, peptides, and aptamers provides the most effective therapy. TNBC is defined by the lack of overexpression of the three common receptors used to classify breast cancer. As a consequence, there are very few available targets. Epidermal growth factor (EGF) is a receptor that promotes cell proliferation migration and angiogenesis (development of new blood vessels). EGFR is overexpressed in many tumors including breast cancer. Hence, many strategies based on antibodies have been studied to block EGFR. The anti-EGFR monoclonal antibody, Cetuximab, has shown promise for targeting metastatic TNBC.
In the present study, Pt NPs are synthesized, and the anticancer activity is tested in vitro against TNBC, showing a remarkable cell death. To achieve better delivery of the particles, Pt NPs are encapsulated within PLGA by nanoemulsion, and surface modifications are performed with PEG and an anti-EGFR to increase circulation time and achieve a higher anticancer effect. Lastly, the particles are tested in vivo, to determine toxicity and biodistribution in mice. Furthermore, realizing the importance of bringing research projects out of the laboratories, Pt NPs are proposed as a potential market product for the NSF I-Corps Northeast Region. In addition, to expand the understanding in entrepreneurship education programs from a diversity and inclusion perspective, experiences of women STEM faculty engaged in biomedical research are examined, using phenomenological experience-based qualitative research.
Recommended Citation
Lopez Ruiz, Aida, "Platinum nanoparticles, targeted therapy for triple negative breast cancer" (2022). Dissertations. 1924.
https://digitalcommons.njit.edu/dissertations/1924
Included in
Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons, Nanoscience and Nanotechnology Commons
