Engineered tumor-homing neural stem cells (NSCs) have shown promise in treating cancer. Recently, we transdifferentiated skin fibroblasts into human-induced NSCs (hiNSC) as personalized NSC drug carriers. Here, using a SOX2 and spheroidal culture-based reprogramming strategy, we generated a new hiNSC variant, hiNeuroS, that was genetically distinct from fibroblasts and first-generation hiNSCs and had significantly enhanced tumor-homing and antitumor properties. In vitro, hiNeuroSs demonstrated superior migration to human triple-negative breast cancer (TNBC) cells and in vivo rapidly homed to TNBC tumor foci following intracerebroventricular (ICV) infusion. In TNBC parenchymal metastasis models, ICV infusion of hiNeuroSs secreting the proapoptotic agent TRAIL (hiNeuroS-TRAIL) significantly reduced tumor burden and extended median survival. In models of TNBC leptomeningeal carcinomatosis, ICV dosing of hiNeuroS-TRAIL therapy significantly delayed the onset of tumor formation and extended survival when administered as a prophylactic treatment, as well as reduced tumor volume while prolonging survival when delivered as established tumor therapy.

a b s t r a c tAnalysis of volatile organic compounds (VOCs) for medical and industrial applications typically requires complex and expensive mass spectrometric systems to achieve the desired sensitivity and specificity. Raman spectroscopy enables specific compound identification based on distinct spectral fingerprints but traditionally has low sensitivity. We have developed a novel Raman system that provides VOC detection in the low ppm range. VOCs from the gas phase are absorbed and enriched in a thin polymer film coated on the surface of an optical sensor element. The VOC enriched polymer film is probed with evanescent wave excitation and optimized Raman signal collection. The herein described Raman sensor is low-cost, robust, readily manufacturable, and capable of providing high sensitivity without the nanostructured sensors required for surface enhanced Raman spectroscopy. To suppress background noise and interfering spectral features while improving our ability to resolve VOC mixture spectra, we applied two-dimensional (2D) correlation analysis to time series spectra acquired during VOC absorption into the polymer film. We established proof of principle through analysis of known VOC biomarkers for selected bacterial pathogens. The system enabled VOC detection with significantly higher sensitivity than commercial Raman probes. We observed good agreement between spectra of VOCs in the thin film obtained after 2D correlation analysis, and of pure VOCs using a commercial probe. Mixture spectra were further de-convoluted based on the off-diagonal peaks observable in the 2D Raman spectrum in conjunction with segmented data analysis. We anticipate that this system can be applied to a variety of medical, industrial, and biodefense applications.

Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for antitumor payloads. However, the in vivo persistence of iNSCs limits their therapeutic potential. We hypothesized that by encapsulating iNSCs in the FDA‐approved, hemostatic matrix FLOSEAL®, we could increase their persistence and, as a result, therapeutic durability. Encapsulated iNSCs persisted for 95 days, whereas iNSCs injected into the brain parenchyma persisted only 2 weeks in mice. Two orthotopic GBM tumor models were used to test the efficacy of encapsulated iNSCs. In the GBM8 tumor model, mice that received therapeutic iNSCs encapsulated in FLOSEAL® survived 30 to 60 days longer than mice that received nonencapsulated cells. However, the U87 tumor model showed no significant differences in survival between these two groups, likely due to the more solid and dense nature of the tumor. Interestingly, the interaction of iNSCs with FLOSEAL® appears to downregulate some markers of proliferation, anti‐apoptosis, migration, and therapy which could also play a role in treatment efficacy and durability. Our results demonstrate that while FLOSEAL® significantly improves iNSC persistence, this alone is insufficient to enhance therapeutic durability.

Quartz crystal microbalance with dissipation monitoring (QCM-D) is a useful technique for observing the adsorption of molecules onto a protein-functionalized surface in real time. This technique is based on relating changes in the frequency of a piezoelectric sensor chip, onto which molecules are adsorbing, to changes in mass using the Sauerbrey equation. Here, we outline the cleaning, preparation, and analysis involved in a typical QCM-D experiment, from which one can obtain mass adsorption and kinetic binding information.

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