Developing Silver Sulfide-Based Nanoparticles for Imaging and Treatment of Breast Cancer Katherine J Mossburg

Format:

Book

Thesis/Dissertation

Author/Creator:

Mossburg, Katherine J., author.

Contributor:

University of Pennsylvania. Bioengineering., degree granting institution.

Language:

English

Subjects (All):

0202.

0541.

0622.

0992.

Local Subjects:

0202.

0541.

0622.

0992.

Physical Description:

1 electronic resource (151 pages)

Contained In:

Dissertations Abstracts International 87-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

Although breast cancer is one of the most common types of cancer, recent advances in treatment and improvements to early screening protocols have significantly decreased mortality. Early detection of tumors using X-ray mammography can drastically improve treatment outcomes, however for patients with dense breasts, this screening tool is not effective. To improve screening options for patients with dense breasts, contrast agents can be used with contrast-enhanced mammography (CEM) for increased sensitivity. Previous work has established sub-5 nm silver sulfide nanoparticles (Ag2S-NP) as promising multimodality contrast agents. Ag2S-NP exhibit improved contrast over standard iodinated agents, longer circulation times, and efficient renal clearance. Inorganic nanoparticles have previously been explored for many biomedical applications but often fail to be clinically translated due to insufficient clearance or safety. To tackle this problem, this study first prepares these promising Ag2S-NP with multiple capping agents (penicillamine, homocysteine, and glutathione) using a library generating microfluidic chip and evaluates their long-term retention and toxicity. Results from this study indicated that glutathione-coated Ag2S-NP provided the ideal combination of in vivo imaging, clearance, and biocompatibility, resulting in its selection for further study. Subsequently, a high throughput system for synthesizing ultrasmall Ag2S-NP was developed using a novel highly parallelized microfluidic chip. Evaluations of Ag2S-NP synthesized with up to 5100x the original output factor revealed that these Ag2S-NP retained their quality and in vivo performance. In conjunction, these efforts resulted in a well-characterized, consistently reproducible contrast agent with a high synthetic yield which can progress toward clinical translation. The study then demonstrates the incorporation of the Ag2S-NP into a larger polymeric nanoparticle platform which facilitates improved tumor accumulation and contrast generation. This platform is also compatible with photothermal therapy, so the nanocarrier can be used as an all-in-one theranostic agent. To improve tumor ablation, the polymeric nanoparticles are also loaded with a heat shock protein inhibitor for release upon laser irradiation. Together, these components provide a comprehensive imaging contrast agent and treatment paradigm for breast cancer. The findings of this thesis indicate a promising future for silver sulfide nanoparticle-based contrast agents across multiple imaging modalities and prepares them for clinical translation

Notes:

Advisors: Cormode, David P. Committee members: Pouch, Alison; Maidment, Andrew D. A.; Issadore, David

Source: Dissertations Abstracts International, Volume: 87-07, Section: B.

Ph.D. University of Pennsylvania 2025

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798276001739

Access Restriction:

Restricted for use by site license