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Improving the physiological relevance of drug testing for drug-loaded nanoparticles using 3D tumor cell cultures

Nanoparticle-mediated drug delivery has the potential to overcome several limitations of cancer chemotherapy. Lipid polymer hybrid nanoparticles (LPHNPs) have been demonstrated to exhibit superior cellular delivery efficacy. Hence, doxorubicin (a chemotherapeutic drug)-loaded LPHNPs have been synthesized by three-dimensional (3D)-printed herringbone-patterned multi-inlet vortex mixer. This method offers rapid and efficient mixing of reactants yielding controllable and reproducible synthesis of LPHNPs. The cytotoxicity of LPHNPs is tested using two-dimensional (2D) and 3D microenvironments. Results obtained from 3D cell cultures showed major differences in cytotoxicity in comparison with 2D cultures. These results have broad implications in predicting in vitro LPHNP toxicology.