TY - JOUR TI - Multifunctional nanoparticle-based approaches to enhance the treatment of cancer DO - https://doi.org/doi:10.7282/T3ZS2ZM4 PY - 2016 AB - Magnetic nanoparticles (MNPs) hold tremendous potential for various biomedical applications, including cancer diagnosis and treatment, owing to their unique ability to be manipulated by magnetic fields. In particular, cancer applications of MNPs have primarily utilized MNPs as MRI contrast agents, drug delivery vehicles, and as agents for magnetic hyperthermia. Significant progress has already been made in the advancement of MNP-based therapies to the clinic; however, tumor targeting and chemoresistance remain significant challenges. Addressing these challenges, this thesis focuses on the development of novel multifunctional MNP-based combination therapies. In the first half of this thesis, novel MNP and magnetic core-shell nanoparticle (MCNP)-based combination therapies are developed to enhance the treatment of cancer by sensitizing cancer cells to subsequent therapies. To this end, MNPs are first developed for the dual purpose of delivering microRNA and inducing magnetic hyperthermia for the treatment of brain cancer. We demonstrate that the combination of lethal-7a microRNA (let-7a), which targets a number of survival pathways, can sensitize cancer cells to subsequent magnetic hyperthermia. Moreover, we demonstrate the use of MCNPs that are composed of a magnetic core and a mesoporous silica shell for the simultaneous delivery of let-7a and doxorubicin, wherein let-7a was found to sensitize breast cancer cells to subsequent doxorubicin chemotherapy. In the second half of this thesis, to overcome poor tumor targeting, a stem cell-based gene therapy is developed. Specifically, MCNPs are reported for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs) for the treatment of ovarian cancer. These engineered AD-MSCs retained their innate ability to home to tumors, making them ideal cellular carriers for cancer therapy. Moreover, mild magnetic hyperthermia resulted in the selective expression of TRAIL in the engineered AD-MSCs thereby inducing significant cancer cell death. Overall, this thesis has demonstrated two multifunctional MNP-based approaches for cancer therapy: 1) combined MNP-based delivery of microRNA and magnetic hyperthermia to sensitize cancers to subsequent chemotherapy and 2) MCNP-based activation of heat-inducible genes in stem cells for targeted cancer treatment. KW - Biomedical Engineering KW - Cancer--Treatment KW - Nanostructures LA - eng ER -