University of Twente Student Theses


Targeting the tumor microenvironment with co-delivery system using electrospun nanofibers

Petrai, Ornela (2021) Targeting the tumor microenvironment with co-delivery system using electrospun nanofibers.

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Embargo date:1 July 2024
Abstract:Cancer is one of the most severe diseases, and many studies have been conducted to investigate possible treatments for it. Cancer is characterized by abnormal cell growth and the ability to invade tissue and distant organs. It is a lethal disease that can eventually cause death if the tumor has progressed beyond the stage that can be removed. Recent treatment mainly includes radiation therapy, surgery, targeted cancer treatment, and chemotherapy are the most used methods for treating various types of cancer. However, these methods usually lead to failures or not complete removal of the tumor site. What is needed is to combine treatment by administrating various drugs that are examined to inhibit and kill tumor cells and minimize the recurrence of cancer once it has been removed. This project mainly focuses on breast cancer treatment even though the same method can be applied to various cancer types. Understanding the importance of the tumor microenvironment (TME) by promoting tumor migration, proliferation, and metastasis and enhancing the drug resistance that is occurred by stromal cells, we also focused on the TME activity. We explored the potential of electrospun nanofibers loaded with two different drugs, one chemotherapy which kills cancer cells, and one antistromal drug which inhibits the cancer-associated fibroblasts that are the most abundant cell type within TME. Electrospinning does not only provide an easy way for controlled drug delivery but also provides local drug delivery, which extends the delivery of the drug at the specific site, minimizing the cytotoxicity to the normal cells and maximizing the drug efficacy. We explore the drug activities on 2D cultured cells and heterospheroids prepared with 3T3 fibroblasts and 4T1 breast tumor cells. Although the potential of paclitaxel is already known, the potential of FRAX597 still needs to be investigated. After the development of electrospun nanofibers and their characterization, dual-drug nanofibers were tested on heterospheroids. Drug-loaded nanofibers caused a significant decrease in the size and growth rate of spheroids. Notably, FRAX597 showed some promising results in cancer treatment, which killed tumor cells more efficiently than chemotherapy. In conclusion, co-therapy nanofibers can inhibit breast cancer cells based on the synergistic action of paclitaxel and the PAK1 inhibitor, FRAX597.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Biomedical Engineering MSc (66226)
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