Improving the physiological relevance of drug testing for drug-loaded nanoparticles using 3D tumor cell cultures
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esearch Letter
Improving the physiological relevance of drug testing for drug-loaded nanoparticles using 3D tumor cell cultures Priya Nimbalkar, Peter Tabada, Anuja Bokare, Jeffrey Chung, Marzieh Mousavi, Melinda Simon, and Folarin Erogbogbo, Department of Biomedical, Chemical, and Materials Engineering, San Jose State University, 1 Washington Square, San Jose, CA 95112, USA Address all correspondence to Folarin Erogbogbo at [email protected] (Received 14 February 2019; accepted 27 June 2019)
Abstract 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.
Introduction Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, the development of multiple drug resistance, and non-specific targeting.[1–4] Nanoparticles (NPs) provide a new mode of cancer drug delivery as a carrier through fenestrations in tumor vasculature allowing direct cell access.[5–7] The focus on nanocarrier design over the years has evolved towards core–shell-type lipid–polymer hybrid nanoparticles (LPHNPs) which have emerged as a robust and promising drug delivery platform.[8–10] LPHNPs are polymeric nanoparticles enveloped by lipid layers, which combine the beneficial characteristics of liposomal drug delivery—cell affinity and cell-targeting ability—with those of polymeric NPs—structural integrity, controlled release, and ease of functionalization to achieve high serum stability.[11] The encapsulation of a drug molecule in these nanocarriers provides effective drug delivery and toxicity reduction.[12] The efficacy of drug delivery therapy depends on a suitable combination of drug and LPHNPs to achieve a synergistic effect on any cancer cell with minimal adverse effects.[13] Doxorubicin is a chemotherapeutic drug that can treat a wide variety of cancers, such as bladder, leukemia, lymphoma, gastric, head and neck, liver, kidney, and cervical and ovarian cancer.[14] The molecular structure of doxorubicin consists of a conjugated ring structure which gives the drug fluorescent properties. Fluorescence allows investigators to track the drug uptake into cells. Moreover, doxorubicin has already been approved for use in NPs under the trade name Doxil.[15]
Hence, incorporating doxoru
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