Fast, low-cost, reliable, and multi-component nanopatterning techniques for functional colloidal nanoparticles have been dreamed about by scientists and engineers for decades. Although countless efforts have been made, it is still a daunting challenge to organize different nanocomponents into a predefined structure with nanometer precision over the millimeter and even larger scale. To meet the challenge, we report a nanoprinting technique that can print various functional colloidal nanoparticles into arbitrarily defined patterns with a 200 nm (or smaller) pitch (>125,000 DPI), 30 nm (or larger) pixel size/linewidth, 10 nm position accuracy and 50 nm overlay precision. The nanopatterning technique combines dielectrophoretic enrichment and deep surface-energy modulation and therefore features high efficiency and robustness. It can form nanostructures over the millimeter-scale by simply spinning, brushing or dip coating colloidal nanoink onto a substrate with minimum error (error ratio < 2 × 10^-6). This technique provides a powerful yet simple construction tool for large-scale positioning and integration of multiple functional nanoparticles toward next-generation optoelectronic and biomedical devices.

Aberrant chromatin remodeling and activation of the PI3K pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of patients with DIPG, we sought to explore radiosensitizing functions of such inhibition and to explore mechanisms of action of such agents. Here, we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models. CUDC-907 modulated DNA damage response by inhibiting radiation-induced DNA repair pathways including homologous recombination and nonhomologous end joining. The radiosensitizing effects of CUDC-907 were mediated by decreased NFκB/Forkhead box M1 (FOXM1) recruitment to promoters of genes involved in the DNA damage response; exogenous expression of NFκB/FOXM1 protected from CUDC-907-induced cytotoxicity. Together, these findings reveal CUDC-907 as a novel radiosensitizer with potent antitumor activity in pHGG and DIPG and provide a preclinical rationale for the combination of CUDC-907 with radiotherapy as a novel therapeutic strategy against pHGG and DIPG. More globally, we have identified NFκB and FOXM1 and their downstream transcriptional elements as critical targets for new treatments for pHGG and DIPG.Significance: These findings describe the radiosensitizing effect of a novel agent in pediatric high-grade gliomas, addressing a critical unmet need of increasing the radiation sensitivity of these highly aggressive tumors. Cancer Res; 78(14); 4007-21. ©2018 AACR.