Glioblastomas (GBMs) are malignant brain tumors associated with lethal cancers that have a great tendency to rapidly invade healthy brain tissue, leaving patients with short survival times and decreased quality of life. The median survival time for patients treated with the chemotherapeutic, temozolomide (TMZ), and radiation therapy is around 12 months, and many patients develop resistance to TMZ due to high activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repairing protein. However, the inclusion of an MGMT inhibitor, such as O6-benzylguanosine (BGS), could work to combat this problem. Currently, the Zhang lab is working on creating nanoparticles (NP) with drug-delivery capabilities, which can cross the blood-brain barrier and deliver chemotherapeutics to targeted glioma cells. This highly drug loaded NP model (IOPH-pBGS) efficiently inhibits MGMT and sensitizes GBM cells to TMZ. However, we wanted to know to what extent a targeting agent would improve this model, and how much efficacy can be increased through optimization of the targeting agent conjugation process. We hypothesized that we can significantly increase drug delivery to tumors by avoiding nonspecific uptake of NPs in healthy cells. My research project was to optimize chlorotoxin (CTX) conjugation to the NPs for use against GBMs. CTX is a small amino-acid peptide sequence that has the ability to target GBM cells. We optimized: the point in the NP synthesis process to add CTX, the length of polyethylene glycol linker to attach CTX to the NP surface, and the reaction ratio of CTX to NP in order to optimize both drug loading and targeting efficacy. In order to evaluate the effectiveness of the various CTX conjugated NPs, SDS-PAGE peptide quantitation assays, cell targeting assays, MGMT quantitation assays and clonogenic cell survival assays were utilized.