M.Sc Thesis


M.Sc StudentAmrusi Yakir
SubjectPersonalized Nanomedicine for Osteosarcoma
DepartmentDepartment of Biomedical Engineering
Supervisor DR. Yosef Shamay
Full Thesis textFull thesis text - English Version


Abstract

Osteosarcoma (OS) is the most common form of bone cancer. It is most prevalent in teenagers and young adults thus, causes a lifelong of problems for the survivors. There is a second incidence peak among individuals over age 60 exists. Males are more likely to suffer from OS at all ages than females. The worldwide incidence of OS is 3.4 cases per million people per year. Current treatments for OS are non-personalized and are based on surgery, radiation, and combinations of chemotherapy, which often results in both toxic side effects and cancer recurrence. 30-50% of the survivors will have a recurrence in 2-3 years after completion of chemotherapeutic treatment. We hypothesized that by encapsulating personalized drugs in nanoparticles (NPs), the drugs can be delivered by both passive and active mechanisms to improve anti-tumor efficacy, drug resistance and toxicity. We show that a subset of sulfated indocyanine dyes can self-assemble with hydrophobic drugs to form stable NPs with high drug loading. An array of drug forming NP were tested on 3 different OS cell lines from different patients and were shown to be patient specific. Furthermore, we show that NPs with various drug combinations can be both personalized and synergistic against multiple OS cell lines. Finally, our data suggest two new general drugs, one is a proteasome inhibitor, and one is chemotherapy which are not used in OS: carfilzomib and paclitaxel as well as certain kinase inhibitors which can be more effective than chemotherapy in some patients. We conclude that functional personalized therapy should be tested in OS patients.