Microfabricated Particles for Engineered Drug Therapies: Elucidation into the Mechanisms of Cellular Internalization of PRINT Particles
| Autor: | Patricia A. Ropp, Joseph M. DeSimone, Mary E. Napier, Stephanie E. A. Gratton, Shaomin Tian |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Drug
media_common.quotation_subject education Pharmaceutical Science Biology Endocytosis Article Mice Pharmaceutical technology Zeta potential Animals Humans Pharmacology (medical) Particle Size Internalization health care economics and organizations media_common Pharmacology Drug Carriers Organic Chemistry Clathrin Cell biology NIH 3T3 Cells Molecular Medicine Particle Particle size Function (biology) Biotechnology HeLa Cells |
| DOI: | 10.17615/wkce-h067 |
| Popis: | To investigate the cellular internalization pathways of shape- and size-specific particles as a function of zeta potential in different cell types.A top-down particle fabrication technique called PRINT was utilized to fabricate monodisperse 1 microm cylindrical particles. Cellular internalization of these PRINT particles was monitored using confocal microscopy, flow cytometry, and transmission electron microscopy. The endocytic pathway used by 1 microm cationic PRINT particles was evaluated using different inhibitory strategies. Cytotoxicity assays were used to determine the toxicity of both cationic and anionic PRINT particles in multiple cell types.Particle internalization was confirmed using confocal microscopy, flow cytometry and transmission electron microscopy. The mechanism of internalization of positively charged PRINT particles was found to be predominantly clathrin-mediated endocytosis and macropinocytosis with very few particles utilizing a caveolae-mediated endocytic pathway. The exposed charge on the surface of the particles had a significant effect on the rate of endocytosis in all cell types tested, except for the macrophage cells. No significant cytotoxicity was observed for all PRINT particles used in the present study.Cylindrical 1 microm PRINT particles were readily internalized into HeLa, NIH 3T3, OVCAR-3, MCF-7, and RAW 264.7 cells. Particles with a positive zeta potential exhibited an enhanced rate of endocytosis compared to negatively charged particles with identical sizes and shapes. It was found that PRINT particles with a positive zeta potential were endocytosed into HeLa cells using predominantely clathrin-mediated and macropinocytotic pathways. |
| Databáze: | OpenAIRE |
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