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Item Atomistic modeling of resistivity evolution of copper nanoparticle in intense pulsed light sintering process(Elsevier, 2019-02) Meng, Lingbin; Zhang, Yi; Yang, Xuehui; Zhang, Jing; Mechanical and Energy Engineering, School of Engineering and TechnologyIn this work, the intense pulsed light (IPL) sintering process of copper nanoparticle ink is simulated using molecular dynamics (MD) method. First, the neck size growth between the two copper nanoparticles during the IPL sintering process is computed. The resultant electrical resistivity is then calculated by substituting the neck size into the Reimann-Weber formula. Overall, a rapid decrease of electric resistivity is observed in the beginning of the sintering, which is caused by quick neck size growth, followed by a gradually decrease of resistivity. In addition, the correlation of the simulated temperature dependent resistivity is similar to that of the experimentally measured resistivity. The MD model is an effective tool for designers to optimize the IPL sintering process.Item Novel therapeutics and drug-delivery approaches in the modulation of glioblastoma stem cell resistance(T&F, 2022-04) Smiley, Shelby B.; Zarrinmayeh, Hamideh; Das, Sudip K.; Pollok , Karen E.; Vannier, Michael W.; Veronesi, Michael C.; Radiology and Imaging Sciences, School of MedicineGlioblastoma (GBM) is a deadly malignancy with a poor prognosis. An important factor contributing to GBM recurrence is high resistance of GBM cancer stem cells (GSCs). While temozolomide (TMZ), has been shown to consistently extend survival, GSCs grow resistant to TMZ through upregulation of DNA damage repair mechanisms and avoidance of apoptosis. Since a single-drug approach has failed to significantly alter prognosis in the past 15 years, unique approaches such as multidrug combination therapy together with distinctive targeted drug-delivery approaches against cancer stem cells are needed. In this review, a rationale for multidrug therapy using a targeted nanotechnology approach that preferentially target GSCs is proposed with discussion and examples of drugs, nanomedicine delivery systems, and targeting moieties.Item Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo(Nature, 2012-04) Kiziltepe, T.; Ashley, J. D.; Stefanick, J. F.; Qi, Y. M.; Alves, Nathan J.; Handlogten, Michael W.; Suckow, M. A.; Navari, R. M.; Bilgicer, B.In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM.