Microfluidic System for Studying the Interaction of Nanoparticles and Microparticles with Cells

Abstract

Nanoparticles and microparticles have many potential biomedical applications ranging from imaging to drug delivery. Therefore, in vitro systems that can analyze and optimize the interaction of such particles with cells may be beneficial. Here, we report a microfluidic system that can be used to study these interactions. As a model system, we evaluated the interaction of polymeric nanoparticles and microparticles and similar particles conjugated to aptamers that recognize the transmembrane prostate specific membrane antigen (PSMA), with cells seeded in microchannels. The binding of particles to cells that expressed or did not express the PSMA (LNCaP or PC3, respectively) were evaluated with respect to changes in fluid shear stress, PSMA expression on target cells, and particle size. Nanoparticle-aptamer bioconjugates selectively adhered to LNCaP but not PC3 cells at static and low shear (<1 dyn/cm2) but not higher shear (approximately 4.5 dyn/cm2) conditions. Control nanoparticles and microparticles lacking aptamers and microparticle-aptamer bioconjugates did not adhere to LNCaP cells, even under very low shear conditions (approximately 0.28 dyn/cm2). These results demonstrate that the interaction of particles with cells can be studied under controlled conditions, which may aid in the engineering of desired particle characteristics. The scalability, low cost, reproducibility, and high-throughput capability of this technology is potentially beneficial to examining and optimizing a wide array of cell-particle systems prior to in vivo experiments.

Drug delivery systems in urology—getting “smarter”

“…23,24 This goal can be achieved through combining controlledrelease technology and targeted drug delivery approaches. With advances in nanotechnology, it is now possible to develop highly selective and effective cancer therapeutics by combining specialized biomaterials with available chemotherapeutic agents.…”

Configurable 2D and 3D spheroid tissue cultures on bioengineered surfaces with acquisition of epithelial–mesenchymal transition characteristics

“…The maximum shear stress for a flow velocity of 240 mm s À1 measured in the beginning of the cell injection was calculated to be 0.5 dyn cm À2 , which is in the low range of shear stress present at different areas of systemic microvasculature. 21 This result indicates that the shear stress adopted in this study by the simple passive microfluidic method could mitigate unwanted physical stimulus to the trapped cells.…”

Clinical applications of nucleic acid aptamers in cancer

“…In an extensive study, following systemic administration, A10-3 aptamer induced tumor accumulation of PLGA NPs by 3.7-fold when compared to the non-targeted particle (72). Further investigations demonstrated that the NP-aptamer bioconjugates may be precisely engineered and formulated by controlling size, composition, polydispersity, aptamer density and drug loading, thereby resulting in the desired functions and biodistribution required for further clinical development (72)(73)(74). Another polymeric formulation has been used to deliver cisplatin to PSMA expressing tumors, whereas a dosage of 0.3 mg̸kg of aptamer-targeted cisplatin NPs was more efficacious compared to a 1 mg̸kg of free cisplatin (75).…”