Doctoral Dissertations

Keywords and Phrases

Breast Cancer; Cancer; Combination Therapy; Nanoparticles; Nanotechnology; Targeted Drug Delivery

Abstract

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug nanorods. The rod shaped nanosized formulation of ADNs significantly enhanced the aqueous phase stability and therapeutic payload of the system while the conjugated mAb was utilized for specific targeting of breast cancer cells. The designed ADN was effective for active targeting and synergistic inhibition of breast cancer cells. The mechanisms of actions of ADN was investigated at the cellular, molecular and genetic levels in cancer cells. The engineered AND synergistically inhibited the growth of > 80% of the human epidermal growth factor receptor 2 (HER2) - positive breast cancer cells in vitro. The cell cycle and protein expression analysis showed that ADN arrested the cellular growth for a prolonged time and induced a programmed cell death mechanism in HER2-positive breast cancer cells in vitro. Finally, the gene regulatory analysis showed the genetic mechanisms of programmed cell death regulation induced by ADN in breast cancer cell lines”--Abstract, page iv.

Advisor(s)

Barua, Sutapa

Committee Member(s)

Forciniti, Daniel
Liu, Yongjian
Wang, Jee-Ching
Yang, Hu

Department(s)

Chemical and Biochemical Engineering

Degree Name

Ph. D. in Chemical Engineering

Publisher

Missouri University of Science and Technology

Publication Date

Fall 2020

Journal article titles appearing in thesis/dissertation

  • Antibody-drug nanoparticles induces synergistic treatment efficacies in breast cancer cells
  • The role of intrinsic signaling pathways in cell proliferation
  • Transcriptional regulation activity of a targeted antibody drug nanorod in breast cancer cells
  • Polymer coated gold-ferric oxide superparamagnetic nanoparticles for theranostic applications
  • Isolation and purification of glycoglycerolipids to induce apoptosis in breast cancer cells

Pagination

xviii, 274 pages

Note about bibliography

Includes bibliographic references.

Rights

© 2020 Muhammad Raisul Abedin, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Thesis Number

T 11768

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