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Nanomedicine for Epigenomic Monitoring and Reprogramming of Cancer Stem Cell

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posted on 2024-06-19, 01:08 authored by Anish Hiresha Verma

Cancer stem cell (CSC) epigenomics serves as a focal hub for crucial information about key cancer hallmarks. These characteristics include fatal attributes such as carcinogenesis, metastasis, and resistance to chemo- and radiotherapy. As a result, it is critical to research the molecular mechanism and treatments to overcome it by tapping into the epigenomic microenvironment of CSCs. Furthermore, CSC epigenomics can be altered (reprogrammed) to improve existing oncology research. However, there is a general dearth of study on CSC epigenomic monitoring or reprogramming. In the first study, we designed a sub-10 nm gold nanoprobes for epigenomic monitoring, which could efficiently penetrate the nucleus of CSCs without inducing any structural changes to the genomic DNA. Furthermore, the nanoprobes produced surface-enhanced Raman signals (SERS) to identify structural, functional, molecular, and proteomic epigenomics. This resulted in the development of a diagnostic tool that uses epigenomic markers to distinguish cancer tissue of origin with 99.5% accuracy. In the second study, ultrasmall gold nanoparticles were developed and demonstrated for the first time the ability to overcome the fundamental limits of nanoprobe interaction with epigenetic methyl group while retaining genomic DNA conformation, which can demethylate the DNA. Benchtop validation and clinical validation successfully demonstrated that ultrasmall gold nanoparticles was responsible for a significant decrease in genetic stemness (DNA methylation), phenotypic stemness (CD44 and CD133 markers), and quiescence (G cell cycle phase) in CSCs. This resulted in causing CSCs to reprogramming back 0 to normal to cancer cells. In the last study, we developed a 3D silica nanostructured matrix with functionality for quick reprogramming of normal cancer cells into CSC spheroids. In vitro benchtop studies in breast, lung, and colon cancer demonstrated that cancer cells transformed into CSC spheroids in 3 days. Overall, the investigation paves the way for the establishment of nanomedicine for monitoring and reprogramming the epigenomic microenvironment of CSCs.

History

Language

eng

Degree

  • Doctor of Philosophy

Program

  • Mechanical and Industrial Engineering

Granting Institution

Ryerson University

LAC Thesis Type

  • Dissertation

Thesis Advisor

Krishnan Venkatakrishnan & Bo Tan

Year

2022

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    Mechanical and Industrial Engineering (Theses)

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