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Protein‐Corona‐by‐Design in 2D: A Reliable Platform to Decode Bio–Nano Interactions for the Next‐Generation Quality‐by‐Design Nanomedicines
Author(s) -
Mei KuoChing,
Ghazaryan Artur,
Teoh Er Zhen,
Summers Huw D.,
Li Yueting,
Ballesteros Belén,
Piasecka Justyna,
Walters Adam,
Hider Robert C.,
Mailänder Volker,
AlJamal Khuloud T.
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201802732
Subject(s) - nanomedicine , nanomaterials , nanotoxicology , quality by design , nanotechnology , materials science , nanoparticle , biophysics , critical quality attributes , nano , chemistry , biology , particle size , composite material
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 ( R 2 = 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 and can serve as a reliable screening platform to uncover HC‐dependent bio–nano interactions to enable the next‐generation quality‐by‐design (QbD) nanomedicines for better clinical translation.