Particle size affects the cellular response in macrophages

• Published in: European journal of pharmaceutical sciences Vol. 41; no. 5; pp. 650 - 657
• Main Authors: Yue, Hua, Wei, Wei, Yue, Zhanguo, Lv, Piping, Wang, Lianyan, Ma, Guanghui, Su, Zhiguo
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 23.12.2010; Elsevier
• Subjects: Animals; Biological and medical sciences; Biological Transport; Biomaterials; Cell Line; Cellular response; Cytokines - secretion; Cytoskeleton - ultrastructure; General pharmacology; Lysosomes - metabolism; Lysosomes - ultrastructure; Macrophage; Macrophages - metabolism; Macrophages - ultrastructure; Medical sciences; Mice; Nanoparticles - chemistry; Particle design; Particle Size; Particulate Matter - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Size; Particle design; Size; Biomaterials; Cellular response; Macrophage; Design; Particle; Particle size; Pharmaceutical technology; Biomaterial; In vitro
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2010.09.006

A deeper understanding of how the physical properties of particles regulate specific biological responses is becoming a crucial requirement for their successful biomedical application. To provide insights on their design and application, J774A.1 cells are exposed to particles with different diameters (430 nm, 1.9 μm and 4.8 μm), and the size effects on a series of cellular responses in macrophages are evaluated. Cellular uptake study demonstrates that nanosized particles accumulate in the cells at a faster rate, and with a higher surface area. Once the data are converted into the expression of particle volume, the maximum value is found with 1.9 μm particles instead of nanoparticles. Moreover, the uptake intermediates are also trapped, and the steps of particle internalization include filopodia sensing, skeleton rearrangement, and morphology change. Subsequent cellular trafficking reveals that only nanosized particles transport via lysosomal pathway, which is consistent with their uptake mechanisms. Furthermore, nanosized particles prefer to promote the secretion of Th1-specific molecule signals (e.g. IFN, IL-12) rather than immune suppressors. All these results, along with a couple of surprises, are discussed in the view of clinical practice. They are expected, in principle, to establish the basis of new design concepts for particle-based biomedical applications.