Kenna Schnarr, Rachael Mooney, Yiming Weng, Donghong Zhao, Elizabeth Garcia, Brian Armstrong, Alexander J. Annala, Seung U. Kim, Karen S. Aboody,* and Jacob M. Berlin* used to add selectivity to this photothermal ablation.[14–17] Selective accumulation of the AuNPs within the tumor allows for the use of a NIR laser to significantly heat AuNPs and surrounding tumor tissue, without appreciably heating or damaging normal tissue. A recent report suggests that with current production techniques gold nanorods (AuNRs) exhibit the best photothermal efficiency as compared to other AuNPs.[18–21] The use of AuNPs thus renders the problem of specific heating to be one of depositing and retaining the AuNPs selectively within the tumor. Currently, passive and active targeting strategies have been attempted for delivery of AuNPs to tumor foci. Most passive strategies depend on the fact that tumors are prone to the accumulation of particles in the size range of approximately 50–200 nm. This is commonly referred to as enhanced permeability and retention (EPR),[22] and it is the result of rapidly growing tumor vasculature being malformed with larger pores, allowing particles to extravasate out. In addition, tumor tissue generally has poor lymphatic drainage, making particles that enter the tumor environment prone to remain there. Active targeting of nanoparticles is accomplished by functionalizing them with ligands, such as monoclonal antibodies, that specifically bind to receptors overexpressed in the tumor environment.[5, 23–26] Using these strategies, progress has been made in NP-mediated targeting of drugs to tumors, but even in the best cases, several major challenges remain for controlling the biodistribution of nanoparticles. In general, nanoparticles predominantly accumulate in the liver and spleen, have difficulty penetrating poorly vascularized hypoxic tumor regions and are unable to cross the blood-brain barrier. Neural Stem Cells (NSCs) are appealing candidates for use as carriers for nanoparticles in order to overcome these biodistribution challenges. NSCs have demonstrated inherent tumor tropic properties in pre-clinical brain and other invasive and metastatic tumor models, migrating selectively to invasive tumor foci, penetrating hypoxic tumor regions, and even traversing the bloodbrain barrier to target intracranial tumor foci following intravenous administration.[27–32] NSCs do not intrinsically have any anti-tumor efficacy, but can be modified to carry various anticancer payloads. One strategy involves genetically modifying NSCs to express an enzyme that will convert a prodrug into the active compound. This approach has been shown to produce a significant tumor-killing effect, decreasing tumor burden and/or increasing long-term survival in mice models.[28, 32–34] Moreover, an established, clonal immortalized human NSC line [35, 36] which expresses cytosine deaminase (HB1. F3. CD) in order to convert

Gold nanoparticles (AuNPs) have shown great promise as a novel therapeutic technology for the treatment of cancer due to their non-cytotoxic nature, ease of synthesis and functionalization and, most importantly, their tunable plasmonic properties.[1–4] This allows AuNPs to be designed such that they cause local heating when exposed to near-infrared (NIR) light.[5] This is significant because of the wavelengths of light, NIR is least absorbed by blood and water, which allows it to penetrate deeply enough into tissue (∼ 4 mm) to be focused on AuNPs for selective photothermal ablation of tumors.[6, 7] Current clinical thermal ablation strategies have shown promise for a number of tumor types, particularly liver and kidney cancers, but are …