عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
TLpq2488183217
انگلیسی
Investigation on Nanoparticle Based Combination Therapy for Targeted Cancer Treatment
[Thesis]
Abedin, Muhammad Raisul
Barua, Sutapa
Missouri University of Science and Technology
2020
294
Ph.D.
Missouri University of Science and Technology
2020
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 nanoparticles 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 ADN 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.
Bioengineering
Cellular biology
Chemical engineering
Genetics
Nanotechnology
Public health
Abedin, Muhammad Raisul
Barua, Sutapa
مطالعه متن کتاب p
[Thesis]
276903
a
Y
