title: Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.
abstract: Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.
authors.affiliation: Department of Chemical Engineering, West Virginia University, WV, USA.
authors.forename: Reem
authors.initials: R
authors.lastname: Eldawud
authors.forename: Manuela
authors.initials: M
authors.lastname: Reitzig
authors.forename: Jörg
authors.initials: J
authors.lastname: Opitz
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojansakul
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Jiang
authors.forename: Shikha
authors.initials: S
authors.lastname: Nangia
authors.forename: Cerasela Zoica
authors.initials: CZ
authors.lastname: Dinu
mesh_terms: D001692:Biological Transport; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002244:Carbon / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D053834:Explosive Agents / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008560:Membrane Fluidity; D008954:Models, Biological; D058612:Nanodiamonds / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D053834:Explosive Agents; D058612:Nanodiamonds; D010713:Phosphatidylcholines; D002244:Carbon; C010942:1,2-distearoyllecithin
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