title: Investigation of biomimetic shear stress on cellular uptake and mechanism of polystyrene nanoparticles in various cancer cell lines.
abstract: Cancer cells in the tumor microenvironment are affected by fluid shear stress generated by blood flow in the vascular microenvironment and interstitial flows in the tumor microenvironment. Thus, we investigated how fluidic shear stress affects cellular uptake as well as the endocytosis mechanism of nanoparticles using a biomimetic microfluidic system that mimics the human dynamic environment. Positively charged amino-modified polystyrene nanoparticles (PSNs) at 100 μg/mL were delivered to cancer cells under static and biomimetic dynamic conditions (0.5 dyne/cm2). Additionally, the experiment was done in the presence of endocytosis inhibitors specific for one of the endocytosis pathways. To evaluate cellular uptake of cationic PSNs, the fluorescence intensity of cationic PSNs in cancer cells was measured by flow cytometer and fluorescence images were taken using confocal laser scanning microscopy. Cancer cells in dynamic conditions exhibited higher cellular uptake of PSNs and showed different cellular uptake mechanisms compared with those in static conditions. From these results, it suggested that biomimetic dynamic conditions stimulated specific endocytosis and prompted cellular uptake. It was also important to consider fluidic shear stress as one of the critical factors because cellular uptake and drug delivery could play a key role in cancer cells and metastasis.
authors.affiliation: College of Pharmacy, Ajou University, Suwon, 16449, Republic of Korea.
authors.forename: Taehee
authors.initials: T
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Ajou University, Suwon, 16449, Republic of Korea.
authors.forename: Chulhun
authors.initials: C
authors.lastname: Park
authors.affiliation: College of Pharmacy, Ajou University, Suwon, 16449, Republic of Korea. bjl@ajou.ac.kr.|Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, 16499, Republic of Korea. bjl@ajou.ac.kr.
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D040761:Biomimetic Materials / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism*; D011137:Polystyrenes / Q000378:metabolism* / Q000494:pharmacology; D033081:Shear Strength / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D011137:Polystyrenes
keywords: Biomimetic microfluidic system; Cancer cell microenvironment; Cellular drug delivery; Endocytosis; Fluidic shear stress; Polystyrene nanoparticles