Engineering Leukocyte Mimicking Nanoparticles for Targeted Delivery in Triple-Negative Breast Cancer: Biological versus Cargo-Based Approach

• Main Author: Sushnitha, Manuela
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2021
• Subjects: Androgens; Apoptosis; Biomedical engineering; Blood; Blood platelets; Breast cancer; Cancer therapies; Chemotherapy; Disease; Drug delivery systems; FDA approval; Immune system; Immunotherapy; Lipids; Membranes; Metastasis; Mutation; Nanoscience; Oncology; Permeability; Pharmacology; Polymers; Proteins; Quantum dots; Radiation therapy; Ratios; Toxicity; Tumors
• ISBN: 9798535524153

Nanoparticles offer the ability to achieve targeted drug delivery across many disease contexts, especially difficult to treat cancers like triple-negative breast cancer (TNBC). The lack of targeted of therapies for TNBC patients has warranted the development of novel strategies for targeting the tumor while delivering therapeutics aimed at targeting the underlying drivers of disease. Recent work has demonstrated the promising potential of nanoparticles to achieve both of these desired functions. However, translation of nanoparticles to the clinic has been hampered by the limited ability of synthetic nanoparticles to overcome the biological barriers posed by the complex in vivo milieu. In order to overcome these limitations, nanoparticles designed to mimic native cells through the integration of cell membrane components have been developed. In particular, leukocyte mimicking lipid nanoparticles have demonstrated the ability to target sites of inflammation, evade immune clearance and deliver therapeutic molecules. Leveraging the advantages of this technology, this study aims to demonstrate the utility of these biomimetic nanoparticles (i.e. leukosomes) for the treatment of TNBC. In particular, engineering of the leukosomes was explored from two perspectives: 1) a biological approach that aimed to improve the tumor targeting abilities of the nanoparticles and 2) a cargo-based approach for the development of a leukosome formulation capable of delivering therapeutic RNA molecules. By combining these two approaches for the engineering of leukocyte mimicking nanoparticles, a novel strategy for targeting and treating TNBC was developed while gaining important insights for the future development of these cell mimicking nanoparticle platforms.