Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions

Author

Ibrahim Nasim, University of Central FloridaFollow

Keywords

cancer; chemotherapy; ultrasound; nucleus; membrane; cell

Abstract

Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how PTX and CP induce cell death via rupture of the nuclear envelope, leading to cell leakage and, eventually, death. NCIH1650 is a cell line derived from the lung tissue of a 27-year-old male smoker with stage 3B bronchoalveolar carcinoma (BAC), a form of non-small cell lung cancer. BAC is characterized by unpredictable growth with a high probability of developing into a rapidly growing tumor. I hypothesize that if the NCIH1650 cell line is treated with PTX and CP in combination, then the treatments will have a synergistic effect, causing micronucleation and quantifiable nuclear rupture, resulting in cell death and lowered proliferation. I approached by grouping the NCIH1650 cells into 4 sections, Control, PTX, CP, and Combination, and either imaged via immunofluorescent staining or analysis of cell number via Water-Soluble Tetrazolium (WST) assay. Additionally, one group of cells was sonicated, and cell counts were measured in 4, 24, and 48-hour intervals. Relative cell counts dropped by 60% with combined treatments applied over a 5-day period but by 70% with combined treatments and sonication when measured 24 hours after sonication. Rupture sites via immunofluorescent imaging were clearly visible in addition to areas of frequent laminopathy, signifying weak structural integrity of the nuclear envelope and subsequent nuclear rupture. Furthermore, approximately 60% of nuclei imaged in treated cells were rupture sites. These findings provide clinical evidence that combining chemotherapy and ultrasound can be effective, minimally invasive treatment. Further in vitro and in vivo studies will be performed to assess better translational possibilities for therapies for patients suffering from lung cancer.

Thesis Completion Year

2025

Thesis Completion Semester

Spring

Thesis Chair

Lu, Shuang

College

College of Health Professions and Sciences

Thesis Discipline

Cancer Biology

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

STARS Citation

Nasim, Ibrahim, "Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions" (2025). Honors Undergraduate Theses. 324.
https://stars.library.ucf.edu/hut2024/324