Plasmonic photothermal therapy utilizes biologically inert gold nanorods (AuNRs) as tumor-localized antennas that convert light into heat capable of eliminating cancerous tissue. This approach has lower morbidity than surgical resection and can potentially synergize with other treatment modalities including chemotherapy and immunotherapy. Despite these advantages, it is still challenging to obtain heating of the entire tumor mass while avoiding unnecessary collateral damage to surrounding healthy tissue. It is therefore critical to identify innovative methods to distribute an effective concentration of AuNRs throughout tumors without depositing them in surrounding healthy tissue. Here we demonstrate that AuNR-loaded, tumor-tropic neural stem cells (NSCs) can be used to improve the intratumoral distribution of AuNRs. A simple UV–vis technique for measuring AuNR loading within NSCs was established. It was then confirmed that NSC viability is unimpaired following AuNR loading and that NSCs retain AuNRs long enough to migrate throughout tumors. We then demonstrate that intratumoral injections of AuNR-loaded NSCs are more efficacious than free AuNR injections, as evidenced by reduced recurrence rates of triple-negative breast cancer (MDA-MB-231) xenografts following NIR exposure. Finally, we demonstrate that the distribution of AuNRs throughout the tumors is improved when transported by NSCs, likely resulting in the improved efficacy of AuNR-loaded NSCs as compared to free AuNRs. These findings highlight the advantage of combining cellular therapies and nanotechnology to generate more effective cancer treatments.

Aim: The purpose of this work is to determine if tumor-tropic neural stem cells (NSCs) can improve the tumor-selective distribution and retention of nanoparticles (NPs) within invasive brain tumors. Materials & methods: Streptavidin-conjugated, polystyrene NPs are surface-coupled to biotinylated human NSCs. These NPs are large (798 nm), yet when conjugated to tropic cells, they are too large to passively diffuse through brain tissue or cross the blood–tumor barrier. NP distribution and retention was quantified 4 days after injections located either adjacent to an intracerebral glioma, in the contralateral hemisphere, or intravenously. Results & conclusion: In all three in vivo injection paradigms, NSC-coupled NPs exhibited significantly improved tumor-selective distribution and retention over free-NP suspensions. These results provide proof-of-principle that NSCs can facilitate the tumor-selective distribution of NPs, a platform useful for improving intracranial drug delivery.

Cancer is one of the leading causes of morbidity and mortality worldwide, with 1,688,780 new cancer cases and 600,920 cancer deaths projected to occur in 2017 in the U.S. alone. Conventional cancer treatments including surgical, chemo‐, and radiation therapies can be effective, but are often limited by tumor invasion, off‐target toxicities, and acquired resistance. To improve clinical outcomes and decrease toxic side effects, more targeted, tumor‐specific therapies are being developed. Delivering anticancer payloads using tumor‐tropic cells can greatly increase therapeutic distribution to tumor sites, while sparing non‐tumor tissues therefore minimizing toxic side effects. Neural stem cells (NSCs) are tumor‐tropic cells that can pass through normal organs quickly, localize to invasive and metastatic tumor foci throughout the body, and cross the blood‐brain barrier to reach tumors in the brain. This review focuses on the potential use of NSCs as vehicles to deliver various anticancer payloads selectively to tumor sites. The use of NSCs in cancer treatment has been studied most extensively in the brain, but the findings are applicable to other metastatic solid tumors, which will be described in this review. Strategies include NSC‐mediated enzyme/prodrug gene therapy, oncolytic virotherapy, and delivery of antibodies, nanoparticles, and extracellular vesicles containing oligonucleotides. Preclinical discovery and translational studies, as well as early clinical trials, will be discussed. Stem Cells Translational Medicine 2018