Protein-Corona-by-Design in 2D: A Reliable Platform to Decode Bio-Nano Interactions for the Next-Generation Quality-by-Design Nanomedicines.

Advanced Materials
Kuo-Ching MeiKhuloud T Al-Jamal

Abstract

Hard corona (HC) protein, i.e., the environmental proteins of the biological medium that are bound to a nanosurface, is known to affect the biological fate of a nanomedicine. Due to the size, curvature, and specific surface area (SSA) 3-factor interactions inherited in the traditional 3D nanoparticle, HC-dependent bio-nano interactions are often poorly probed and interpreted. Here, the first HC-by-design case study in 2D is demonstrated that sequentially and linearly changes the HC quantity using functionalized graphene oxide (GO) nanosheets. The HC quantity and HC quality are analyzed using NanoDrop and label-free liquid chromatography-mass spectrometry (LC-MS) followed by principal component analysis (PCA). Cellular responses (uptake and cytotoxicity in J774 cell model) are compared using imaging cytometry and the modified lactate dehydrogenase assays, respectively. Cellular uptake linearly and solely correlates with HC quantity (R2 = 0.99634). The nanotoxicity, analyzed by retrospective design of experiment (DoE), is found to be dependent on the nanomaterial uptake (primary), HC composition (secondary), and nanomaterial exposure dose (tertiary). This unique 2D design eliminates the size-curvature-SSA multifactor interactions...Continue Reading

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Citations

Jan 29, 2019·Current Topics in Medicinal Chemistry·Yanan LiFeifei An
Jul 26, 2019·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Zilei GuoXiaoyuan Ji
Jun 11, 2021·Analytical Chemistry·Fan XuPengfei Wang
Jul 17, 2019·ACS Applied Materials & Interfaces·Rahul M VisalakshanKrasimir Vasilev

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Methods Mentioned

BETA
biosensing
transmission electron microscopy
PCA

Software Mentioned

Design
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